Author: "Jean-Luc Ravanat" / Topic: animals - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Jean-Luc Ravanat"' showing total 55 results

Start Over Author "Jean-Luc Ravanat" Topic animals

55 results on '"Jean-Luc Ravanat"'

1. Impact of nanoparticles on DNA repair processes: current knowledge and working hypotheses

Author: Jean-Luc Ravanat, Marie Carrière, Thierry Douki, Sylvie Sauvaigo, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), and LXRepair
Subjects: 0301 basic medicine, DNA Repair, DNA damage, Computer science, DNA repair, Health, Toxicology and Mutagenesis, Gene induction, Computational biology, Working hypothesis, Toxicology, medicine.disease_cause, 03 medical and health sciences, DNA Repair Protein, Genetics, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics (clinical), Protein function, DNA, Review article, 030104 developmental biology, Nanoparticles, Genotoxicity, DNA Damage
Abstract: International audience; The potential health effects of exposure to nanomaterials (NMs) is currently heavily studied. Among the most often reported impact is DNA damage, also termed genotoxicity. While several reviews relate the DNA damage induced by NMs and the techniques that can be used to prove such effects, the question of impact of NMs on DNA repair processes has never been specifically reviewed. The present review article proposes to fill this gap of knowledge by critically describing the DNA repair processes that could be affected by nanoparticle (NP) exposure, then by reporting the current state of the art on effects of NPs on DNA repair, at the level of protein function, gene induction and post-transcriptional modifications, and taking into account the advantages and limitations of the different experimental approaches. Since little is known about this impact, working hypothesis for the future are then proposed.
Published: 2016
Full Text: View/download PDF

2. Depleted uranium induces sex- and tissue-specific methylation patterns in adult zebrafish

Author: Sandrine Pereira, Virginie Camilleri, Jean-Paul Bourdineaud, Kewin Gombeau, Isabelle Cavalie, Christelle Adam-Guillermin, Jean-Luc Ravanat, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Environnements et Paléoenvironnements OCéaniques (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Recherche commun IRSN-CNRS-Lille1 'Cinétique Chimique, Combustion, Réactivité' (C3R), Université de Lille, Sciences et Technologies-Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École Pratique des Hautes Études (EPHE)
Subjects: Male, 0301 basic medicine, Water Pollutants, Radioactive, HpaII, Health, Toxicology and Mutagenesis, 010501 environmental sciences, medicine.disease_cause, Methylation, 01 natural sciences, Andrology, 03 medical and health sciences, Sex Factors, Tandem Mass Spectrometry, medicine, Animals, Environmental Chemistry, Epigenetics, Waste Management and Disposal, Zebrafish, Chromatography, High Pressure Liquid, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, Demethylation, Genetics, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, General Medicine, biology.organism_classification, Pollution, 030104 developmental biology, Organ Specificity, Toxicity, DNA methylation, Uranium, Female, Oxidative stress
Abstract: We examined the effects of chronic exposure to different concentrations (2 and 20 μg L(-)(1)) of environmentally relevant waterborne depleted uranium (DU) on the DNA methylation patterns both at HpaII restriction sites (5'-CCGG-3') and across the whole genome in the zebrafish brain, gonads, and eyes. We first identified sex-dependent differences in the methylation level of HpaII sites after exposure. In males, these effects were present as early as 7 days after exposure to 20 μg L(-)(1) DU, and were even more pronounced in the brain, gonads, and eyes after 24 days. However, in females, hypomethylation was only observed in the gonads after exposure to 20 μg L(-)(1) DU for 24 days. Sex-specific effects of DU were also apparent at the whole-genome level, because in males, exposure to 20 μg L(-)(1) DU for 24 days resulted in cytosine hypermethylation in the brain and eyes and hypomethylation in the gonads. In contrast, in females, hypermethylation was observed in the brain after exposure to both concentrations of DU for 7 days. Based on our current knowledge of uranium toxicity, several hypotheses are proposed to explain these findings, including the involvement of oxidative stress, alteration of demethylation enzymes and the calcium signaling pathway. This study reports, for the first time, the sex- and tissue-specific epigenetic changes that occur in a nonhuman organism after exposure to environmentally relevant concentrations of uranium, which could induce transgenerational epigenetic effects.
Published: 2016
Full Text: View/download PDF

3. Dose-dependent genomic DNA hypermethylation and mitochondrial DNA damage in Japanese tree frogs sampled in the Fukushima Daiichi area

Author: Jean-Marc Bonzom, Kewin Gombeau, Thierry Lengagne, Daniel Orjollet, Jean-Paul Bourdineaud, Jean-Luc Ravanat, Nicolas Dubourg, Olivier Armant, Virginie Camilleri, Christelle Adam-Guillermin, Isabelle Cavalie, Karine Beaugelin-Seiller, Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Laboratoire de recherche sur les transferts des radionucléides dans les écosystèmes terrestres (IRSN/PSE-ENV/SRTE/LR2T), Microbiologie Fondamentale et Pathogénicité (MFP), Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés (LEHNA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de micro-irradiation, de métrologie et de dosimétrie neutrons (IRSN/PSE-SANTE/SDOS/LMDN), Service de dosimétrie (IRSN/PSE-SANTE/SDOS), Institut de Radioprotection et de sûreté nucléaire PSE-ENV/SRTE/LECO (IRSN), Institut de Radioprotection et de sûreté Nucléaire (PSE-ENV/SRTE/LR2T (URSN), Microbiologie Fondamentale et Pathogénicité [Bordeaux] (MFP), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and INSN, PSE-SANTE/SDOS/LMDN
Subjects: Genome instability, Mitochondrial DNA, 010504 meteorology & atmospheric sciences, Health, Toxicology and Mutagenesis, Zoology, 010501 environmental sciences, Biology, Radiation Dosage, DNA, Mitochondrial, 01 natural sciences, chemistry.chemical_compound, Japan, Radiation Monitoring, Animals, Fukushima Nuclear Accident, Environmental Chemistry, Ecotoxicology, Japanese tree frog-Dryophytes japonicus, Fukushima, Waste Management and Disposal, 0105 earth and related environmental sciences, mitochondrial DNA damage, Dose-Response Relationship, Radiation, Genomics, General Medicine, Methylation, DNA Methylation, Pollution, genomic DNA, Fukushima daiichi, chemistry, Cesium Radioisotopes, 13. Climate action, DNA methylation, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, ionizing radiation, DNA, DNA Damage
Abstract: International audience; The long-term consequences of the nuclear disaster at the Fukushima Daiichi Nuclear Power Plant (FDNPP) that occurred on March 2011, have been scarcely studied on wildlife. We sampled Japanese tree frogs (Dryophytes japonicus), in a 50-km area around the FDNPP to test for an increase of DNA damages and variation of DNA methylation level. The ambient dose rate ranged between 0.4 and 2.8 µGy h-1 and the total estimated dose rate absorbed by frogs ranged between 0.4 and 4.9 µGy h-1. Frogs from contaminated sites exhibited a dose dependent increase of global genomic DNA methylation level (5-mdC and 5-hmdC) and of mitochondrial DNA damages. Such DNA damages may indicate a genomic instability, which may induce physiological adaptations governed by DNA methylation changes. This study stresses the need for biological data combining targeted molecular methods and classic ecotoxicology, in order to better understand the impacts on wildlife of long term exposure to low ionizing radiation levels.
Published: 2020
Full Text: View/download PDF

4. Natural variability and modulation by environmental stressors of global genomic cytosine methylation levels in a freshwater crustacean, Gammarus fossarum

Author: Thérèse Bastide, Nicolas Delorme, Pauline Cribiu, Jean-Luc Ravanat, Hervé Quéau, Alain Devaux, Sylvain Caillat, Arnaud Chaumot, Olivier Geffard, Sylvie Bony, Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés (LEHNA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), École Nationale des Travaux Publics de l'État (ENTPE), École Nationale des Travaux Publics de l'État (ENTPE)-Ministère de l'Ecologie, du Développement Durable, des Transports et du Logement, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), 'Ministere de la transition ecologique et solidaire' (France), 'Institut National de Recherche en Sciences et Technologies pour l'Environnement et l'Agriculture' (France), 'Institut National de la Recherche Agronomique' (France), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)
Subjects: 0301 basic medicine, Range (biology), Health, Toxicology and Mutagenesis, Sentinel species, Zoology, Fresh Water, Aquatic Science, Ecotoxicology, 03 medical and health sciences, Cytosine, Animals, Amphipoda, 14. Life underwater, Epigenetics, ComputingMilieux_MISCELLANEOUS, Invertebrate, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Stressor, Environmental stressor, Genomics, DNA Methylation, biology.organism_classification, Crustacean, EPIGENETICS, 030104 developmental biology, GAMMARUS FOSSARUM, 13. Climate action, DNA methylation, [SDE]Environmental Sciences, ENVIRONMENTAL STRESSOR, Biomarkers, Water Pollutants, Chemical, Cadmium
Abstract: [Departement_IRSTEA]Eaux [TR1_IRSTEA]BELCA [ADD1_IRSTEA]Systèmes aquatiques soumis à des pressions multiples; International audience; To improve the assessment of aquatic organism responses to environmental stressors, there is an interest in studying epigenetic marks in addition to other validated biomarkers. Indeed, the epigenetic marks may be influenced by the surrounding environment. Non-model invertebrates such as gammarids are sentinel organisms representative of the diversity of natural stream communities. Despite their ecologically relevance, the epigenetic responses have been to date poorly documented in these species. The present study explores the measurement of the global cytosine methylation level in the genome of the freshwater crustacean Gammarus fossarum. In a first step, natural variability of global cytosine methylation level (basal level) was assessed by studying the effect of sex, age and sampling site of organisms. Results showed a significant effect of age and sampling site. In a second step, effects of water temperature and food starvation were studied. For both factors, a hypermethylation was observed after 1 month of exposure. In a third step, gammarids were exposed to a range of environmentally relevant cadmium concentrations (0.05-5 µg/L) in order to assess the effect of a chemical stress. Whatever the cadmium concentration used, a significant hypomethylation was observed after 14 days followed by a trend for hypermethylation after 1 month of exposure. These results are the first ones dealing with the 5Cmethylation status in gammarids. The results constitute potential markers of environmental stresses in relevant sentinel species widely used in ecotoxicological studies.
Published: 2018
Full Text: View/download PDF

5. Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes

Author: Mohamed G. Atta, Jean-Philippe Deglasse, Diego Balboa, Stéphane Demine, Ewan R. Pearson, Sanna Toivonen, Esteban Diaz Villamil, Timo Otonkoski, Andrea Alex Schiavo, Piero Marchetti, Jean-Christophe Jonas, Cristina Cosentino, Mariana Igoillo-Esteve, Nathalie Pachera, Jean-Luc Ravanat, Decio L. Eizirik, Miriam Cnop, Université libre de Bruxelles (ULB), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche Expérimentale et Clinique-Pôle d'Endocrinologie, Diabétologie, et Nutrition (EDIN), Université Catholique de Louvain = Catholic University of Louvain (UCL), Research Programs [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Pediatric Research Center [Helsinki], Ninewells Hospital and Medical School [Dundee], Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, Department of Clinical and Experimental Medicine [Pisa, Italy], University of Pisa [Italy], Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles (ULB), Centre of Excellence in Stem Cell Metabolism, Research Programme for Molecular Neurology, Timo Pyry Juhani Otonkoski / Principal Investigator, Research Programs Unit, Faculty of Medicine, University of Helsinki, Children's Hospital, Clinicum, HUS Children and Adolescents, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, and University of Pisa - Università di Pisa
Subjects: 0301 basic medicine, INTELLECTUAL DISABILITY, Diabetes Mellitus -- genetics -- metabolism, Genetic Linkage, Apoptosis, chemistry.chemical_compound, Diabetes mellitus genetics, 0302 clinical medicine, ENDOPLASMIC-RETICULUM STRESS, RNA, Transfer, RNA interference, Insulin-Secreting Cells, Protein biosynthesis, Cells, Cultured, Apoptosis -- genetics, Cell Death, Nucleic Acid Enzymes, METHYLATION, Translation (biology), Cell Differentiation, Sciences bio-médicales et agricoles, Middle Aged, 3. Good health, Cell biology, GENOME, Transfer RNA, Cell Death -- genetics, Induced Pluripotent Stem Cells, Guanosine, Methyltransferases -- deficiency -- genetics -- metabolism, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, DNA Fragmentation, Biology, RNA, Transfer -- metabolism, Induced Pluripotent Stem Cells -- physiology, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Diabetes Mellitus, Genetics, Animals, Humans, Aged, Cell Differentiation -- genetics, IDENTIFICATION, TRNA Methyltransferase, RNA, CDKAL1, Methyltransferases, DNA Methylation, GENE, Rats, 030104 developmental biology, chemistry, Mutation, 1182 Biochemistry, cell and molecular biology, 3111 Biomedicine, TRANSLATION, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Insulin-Secreting Cells -- metabolism -- physiology
Abstract: Transfer RNAs (tRNAs) are non-coding RNA molecules essential for protein synthesis. Post-transcriptionally they are heavily modified to improve their function, folding and stability. Intronic polymorphisms in CDKAL1, a tRNA methylthiotransferase, are associated with increased type 2 diabetes risk. Loss-of-function mutations in TRMT10A, a tRNA methyltransferase, are a monogenic cause of early onset diabetes and microcephaly. Here we confirm the role of TRMT10A as a guanosine 9 tRNA methyltransferase, and identify tRNAGln and tRNAiMeth as two of its targets. Using RNA interference and induced pluripotent stem cell-derived pancreatic β-like cells from healthy controls and TRMT10A-deficient patients we demonstrate that TRMT10A deficiency induces oxidative stress and triggers the intrinsic pathway of apoptosis in β-cells. We show that tRNA guanosine 9 hypomethylation leads to tRNAGln fragmentation and that 5'-tRNAGln fragments mediate TRMT10A deficiency-induced β-cell death. This study unmasks tRNA hypomethylation and fragmentation as a hitherto unknown mechanism of pancreatic β-cell demise relevant to monogenic and polygenic forms of diabetes., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2018
Full Text: View/download PDF

6. Enhancement of IUdR Radiosensitization by Low-Energy Photons Results from Increased and Persistent DNA Damage

Author: Jonathan Dadoun, Jean Bourhis, Eric Deutsch, L. Calmels, Fabien Allot, Marc Denoziere, Johann Plagnard, Frederic Pouzoulet, Emilie Bayart, Jean-Luc Ravanat, André Bridier, Unité de radiothérapie moléculaire ( UMR 1030 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Plateforme de Radiothérapie Expérimentale, Département de Recherche Translationnelle, Institut Curie-Institut Curie, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy ( IGR ), Laboratoire National Henri Becquerel ( BNM/LNHB ), Laboratoire National Henri Becquerel (BNM/LNHB), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie ( CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé ( SYMMES ), Institut Nanosciences et Cryogénie ( INAC ), Université Grenoble Alpes ( UGA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes ( UGA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut Nanosciences et Cryogénie ( INAC ), Université Grenoble Alpes ( UGA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes ( UGA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ), Radiation Oncology Service, Centre Hospitalier Universitaire Vaudois [Lausanne] ( CHUV ), Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, ANR-10-BLAN-1532,RAPHAELO,Radiothérapie par Photo-Activation d'Eléments LOurds ( 2010 ), Radiothérapie moléculaire (UMR 1030), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris]-Institut Curie [Paris], Institut Gustave Roussy (IGR), Laboratoire National Henri Becquerel (LNHB), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), ANR-10-BLAN-1532,RAPHAELO,Radiothérapie par Photo-Activation d'Eléments LOurds(2010), Rayet, Béatrice, BLANC - Radiothérapie par Photo-Activation d'Eléments LOurds - - RAPHAELO2010 - ANR-10-BLAN-1532 - BLANC - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Département d'instrumentation Numérique (DIN (CEA-LIST))
Subjects: IODODEOXYURIDINE IUDR, Radiation-Sensitizing Agents, medicine.medical_treatment, Cancer Treatment, lcsh:Medicine, DOUBLE-STRAND BREAKS, Biochemistry, Radiation Tolerance, 030218 nuclear medicine & medical imaging, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Pyrimidine analogue, chemistry.chemical_compound, 0302 clinical medicine, HUMAN FIBROBLASTS, Medicine and Health Sciences, lcsh:Science, Multidisciplinary, Physics, X-ray, Nucleic acids, Chemistry, Oncology, Cesium Radioisotopes, 030220 oncology & carcinogenesis, Physical Sciences, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Engineering and Technology, HIGH-LET RADIATION, Tumor Suppressor p53-Binding Protein 1, [CHIM.RADIO]Chemical Sciences/Radiochemistry, [ CHIM.RADIO ] Chemical Sciences/Radiochemistry, Elementary Particles, Research Article, Chemical Elements, Iodine, Clinical Oncology, DNA repair, DNA damage, Cell Survival, CELL LUNG-CANCER, RTOG 86-12, Biophysics, Radiation Therapy, Equipment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiation, Animals, Cell Line, Tumor, Cell Survival/drug effects, DNA Damage/drug effects, Dose-Response Relationship, Radiation, Humans, Idoxuridine/pharmacology, Kinetics, Photons, Radiation Tolerance/drug effects, Radiation-Sensitizing Agents/pharmacology, Rats, Synchrotrons, Tumor Suppressor p53-Binding Protein 1/metabolism, X-Rays, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, CHROMOSOME-DAMAGE, Dosimetry, Idoxuridine, cancer, radioactivity, ionizing radiation, photons, radiotherapy, irradiation, radiosensitization, low-energy X-ray therapy, [CHIM.RADIO] Chemical Sciences/Radiochemistry, [ PHYS.PHYS.PHYS-MED-PH ] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], medicine, Genetics, HALOGENATED PYRIMIDINES, Irradiation, Particle Physics, [PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Biology and life sciences, business.industry, lcsh:R, DNA, Radiation therapy, chemistry, X-RAY, lcsh:Q, Clinical Medicine, Particle Accelerators, Nuclear medicine, business, ACTIVATION THERAPY
Abstract: International audience; Low-energy X-rays induce Auger cascades by photoelectric absorption in iodine present in the DNA of cells labeled with 5-iodo-2'-deoxyuridine (IUdR). This photoactivation therapy results in enhanced cellular sensitivity to radiation which reaches its maximum with 50 keV photons. Synchrotron core facilities are the only way to generate such monochromatic beams. However, these structures are not adapted for the routine treatment of patients. In this study, we generated two beams emitting photon energy means of 42 and 50 keV respectively, from a conventional 225 kV X-ray source. Viability assays performed after pre-exposure to 10 μM of IUdR for 48h suggest that complex lethal damage is generated after low energy photons irradiation compared to 137 Cs irradiation (662KeV). To further decipher the molecular mechanisms leading to IUdR-mediated radiosensitization, we analyzed the content of DNA damage-induced foci in two glioblastoma cell lines and showed that the decrease in survival under these conditions was correlated with an increase in the content of DNA damage-induced foci in cell lines. Moreover, the follow-up of repair kinetics of the induced double-strand breaks showed the maximum delay in cells labeled with IUdR and exposed to X-ray irradiation. Thus, there appears to be a direct relationship between the reduction of radiation survival parameters and the production of DNA damage with impaired repair of these breaks. These results further support the clinical potential use of a haloge-nated pyrimidine analog combined with low-energy X-ray therapy.
Published: 2017
Full Text: View/download PDF

7. Epigenetic, histopathological and transcriptomic effects following exposure to depleted uranium in adult zebrafish and their progeny

Author: Jean-Paul Bourdineaud, Virginie Camilleri, Kewin Gombeau, Christelle Adam-Guillermin, Isabelle Cavalie, Jean-Luc Ravanat, Olivier Armant, Magali Floriani, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Environnements et Paléoenvironnements OCéaniques (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Karlsruhe Institute of Technology (KIT), Laboratoire de Recherche commun IRSN-CNRS-Lille1 'Cinétique Chimique, Combustion, Réactivité' (C3R), Université de Lille, Sciences et Technologies-Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École Pratique des Hautes Études (EPHE), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: 0301 basic medicine, Water Pollutants, Radioactive, animal structures, Embryo, Nonmammalian, Health, Toxicology and Mutagenesis, 010501 environmental sciences, Aquatic Science, Eye, 01 natural sciences, Epigenesis, Genetic, Transcriptome, Andrology, 03 medical and health sciences, Myosin, Gene expression, Animals, Epigenetics, Muscle, Skeletal, Zebrafish, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Embryo, Cell cycle, biology.organism_classification, Molecular biology, 030104 developmental biology, Larva, embryonic structures, DNA methylation, Uranium, Female, Water Pollutants, Chemical, Photoreceptor Cells, Vertebrate
Abstract: This study investigated the effects of adult zebrafish exposure to a nominal concentration of 20μgL-1 of depleted uranium (DU) for six days upon DNA methylation, gene expression and the appearance of histopathological damage in their progeny. In the embryos at the 2-8 cell stage, the parental exposure induced significant DU accumulation, with levels seven times higher than those measured in the control embryos, but in larvae 96h post-fertilisation (hpf), uranium concentration had already returned to a level identical to that of the control larvae. A significant two-fold increase in the global level of DNA methylation was observed in embryos as early as the prim5 (24 hpf) stage and was still maintained at the 96 hpf stage despite the fact that DU had already been depurated at the later stage. RNA sequencing analysis indicated an impact of parental exposure upon the total RNAs transmitted from the mother to eggs, and the up-regulated genes were those associated with post-traductional protein modification and trafficking and cellular signalling pathways, whereas the down-regulated genes concerned the translational process, cell cycle regulation and several cell signalling pathways. Alterations of photoreceptor cells and the axon-axon junctions between photoreceptors were observed in the eyes of adult fish exposed for 10days to DU. Actin and myosin filament disorganisation was observed in the skeletal muscles of 96 hpf larvae, at a stage when the maternally transmitted DU had already been excreted. These data reveal the extreme sensitivity of zebrafish embryos to DU transmitted through the oocyte by exposed females.
Published: 2016
Full Text: View/download PDF

8. A combined proteomic and targeted analysis unravels new toxic mechanisms for zinc oxide nanoparticles in macrophages

Author: Jean-Luc Ravanat, Thierry Rabilloud, Bastien Dalzon, Jean Marc Strub, Véronique Collin-Faure, Hélène Diemer, Marie Carrière, Alain Van Dorsselaer, Catherine Aude-Garcia, Sarah Cianférani, Protéomique, Métaux et Différenciation (ProMD ), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Proteomics, Cell signaling, Proteome, DNA damage, Zirconium dioxide, Biophysics, 02 engineering and technology, MESH: Zinc Oxide, Mitochondrion, Biochemistry, Cell Line, Mice, 03 medical and health sciences, chemistry.chemical_compound, Phagocytosis, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Zinc oxide, Animals, MESH: Animals, MESH: Mice, Glutathione biosynthesis, biology, Macrophages, MESH: Proteomics, Methylglyoxal, MESH: Macrophages, 021001 nanoscience & nanotechnology, Aryl hydrocarbon receptor, Methyglyoxal, Mitochondria, MESH: Cell Line, Heme oxygenase, MESH: Proteome, 030104 developmental biology, chemistry, Cell culture, Cancer cell, biology.protein, Nanoparticles, 0210 nano-technology, MESH: Nanoparticles
Abstract: The cellular responses of the J774 macrophage cell line to zinc oxide and zirconium oxide nanoparticles have been studied by a comparative quantitative, protein level based proteomic approach. The most prominent results have been validated by targeted approaches. These approaches have been carried out under culture conditions that stimulate mildly the aryl hydrocarbon receptor, thereby mimicking conditions that can be encountered in vivo in complex environments. The comparative approach with two nanoparticles allows to separate the common responses, which can be attributed to the phagocytosis event per se, from the response specific to each type of nanoparticles. The zinc-specific responses are the most prominent ones and include mitochondrial proteins too, but also signaling molecules such as MyD88, proteins associated with methylglyoxal detoxification (glyoxalase 2, aldose reductase) and deoxyribonucleotide hydrolases. The in cellulo inhibition of GAPDH by zinc was also documented, representing a possible source of methylglyoxal in the cells, leading to an increase in methylglyoxal-modified DNA bases. These observations may be mechanistically associated with the genotoxic effect of zinc and its selective effects on cancer cells.The responses of the murine J774 macrophage cell lines to two types of metallic oxide nanoparticles (zinc oxide and zirconium dioxide) were studied by a comparative 2D gel based approach. This allows sorting of shared responses from nanoparticle-specific responses. Zinc oxide nanoparticles induced specifically a strong decrease in the mitochondrial function, in phagocytosis and also an increase in the methylglyoxal-associated DNA damage, which may explain the well known genotoxicity of zinc. In conclusion, this study allows highlighting of pathways that may play an important role in the toxicity of the zinc oxide nanoparticles.
Published: 2016
Full Text: View/download PDF

9. Oxidatively generated base damage to cellular DNA

Author: Jean Cadet, Thierry Douki, Jean-Luc Ravanat, Douki, Thierry, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: [CHIM.ANAL] Chemical Sciences/Analytical chemistry, Radical, 010402 general chemistry, Tandem mass spectrometry, Photochemistry, medicine.disease_cause, 01 natural sciences, Biochemistry, Redox, Nucleobase, 03 medical and health sciences, chemistry.chemical_compound, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Tandem Mass Spectrometry, Radiation, Ionizing, Physiology (medical), medicine, Animals, Humans, Chromatography, High Pressure Liquid, 030304 developmental biology, 0303 health sciences, Singlet oxygen, Nucleosides, Oxidants, DNA extraction, 0104 chemical sciences, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Oxidative Stress, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Hydroxyl radical, Lipid Peroxidation, Oxidative stress, DNA Damage
Abstract: Search for the formation of oxidatively base damage in cellular DNA has been a matter of debate for more than 40 years due to the lack of accurate methods for the measurement of the lesions. HPLC associated with either tandem mass spectrometry (MS/MS) or electrochemical detector (ECD) together with optimized DNA extraction conditions constitutes a relevant analytical approach. This has allowed the accurate measurement of oxidatively generated single and clustered base damage in cellular DNA following exposure to acute oxidative stress conditions mediated by ionizing radiation, UVA light and one-electron oxidants. In this review the formation of 11 single base lesions that is accounted for by reactions of singlet oxygen, hydroxyl radical or high intensity UVC laser pulses with nucleobases is discussed on the basis of the mechanisms available from model studies. In addition several clustered lesions were found to be generated in cellular DNA as the result of one initial radical hit on either a vicinal base or the 2-deoxyribose. Information on nucleobase modifications that are formed upon addition of reactive aldehydes arising from the breakdown of lipid hydroperoxides is also provided.
Published: 2010
Full Text: View/download PDF

10. Sensitized formation of oxidatively generated damage to cellular DNA by UVA radiation

Author: Jean-Luc Ravanat, Jean Cadet, Thierry Douki, Paolo Di Mascio, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Universidade de Sao Paolo, Douki, Thierry, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: [CHIM.ANAL] Chemical Sciences/Analytical chemistry, UVA Radiation, Pyrimidine, Oxidative degradation, Ultraviolet Rays, DNA damage, Cells, Oxidative phosphorylation, 010402 general chemistry, Photochemistry, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Cellular dna, Animals, Humans, Physical and Theoretical Chemistry, 030304 developmental biology, 0303 health sciences, Photosensitizing Agents, DNA, 0104 chemical sciences, [SDV.TOX] Life Sciences [q-bio]/Toxicology, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Hydroxyl radical, sense organs, Oxidation-Reduction, DNA Damage
Abstract: The survey is aimed at critically reviewing information on the UVA-mediated oxidative reactions to cellular components with emphasis on DNA as the result of mostly photosensitized pathways. It appears clearly that UVA radiation is relatively much more efficient than UVB photons in inducing oxidative processes. The main UVA-induced oxidative degradation pathways of DNA are reported and discussed mechanistically. They are mostly rationalized in terms of a major contribution of singlet molecular oxygen ((1)O(2)) and to a lesser extent of hydroxyl radical ( OH), that in the latter case originates from Fenton-type reactions. This leads to the predominant formation of 8-oxo-7,8-dihydroguanine together with smaller amounts of oxidized pyrimidine bases and DNA strand breaks in UVA-irradiated cells.
Published: 2009
Full Text: View/download PDF

11. Cadmium and T cell differentiation: Limited impact in vivo but significant toxicity in fetal thymus organ culture

Author: V. Collin-Faure, Muriel Viau, Pierre Richaud, Serge M. Candéias, Jean-Luc Ravanat, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biochimie et biophysique des systèmes intégrés (BBSI), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Biologie cellulaire et moléculaire des plantes et des bactéries (BCMPB), Université de la Méditerranée - Aix-Marseille 2-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de la Méditerranée - Aix-Marseille 2, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: DNA repair, T-Lymphocytes, T cell, Cellular differentiation, Population, Apoptosis, Thymus Gland, Biology, Toxicology, Mice, 03 medical and health sciences, Organ Culture Techniques, 0302 clinical medicine, Cadmium Chloride, Pregnancy, medicine, Animals, Tissue Distribution, education, Cells, Cultured, 030304 developmental biology, Pharmacology, 0303 health sciences, education.field_of_study, Cell Differentiation, T lymphocyte, Cell cycle, Carcinogens, Environmental, 3. Good health, Cell biology, Mice, Inbred C57BL, Thymocyte, medicine.anatomical_structure, Gamma Rays, [SDV.TOX]Life Sciences [q-bio]/Toxicology, 030220 oncology & carcinogenesis, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Spleen, DNA Damage, Nucleotide excision repair
Abstract: International audience; DNA lesions, including oxydated bases, nucleotide damage and double strand breaks, are continuously produced in living cells and represent a threat for genetic stability. Highly conserved repair processes have evolved to maintain DNA integrity. Cadmium (Cd) is an environmental carcinogenic pollutant known to inactivate several proteins involved in DNA repair systems while at the same time creating an oxidative stress that can result in additional DNA lesions. Cd also has potent immunotoxic effects. DNA repair by non-homologous end joining (NHEJ) is absolutely required for T lymphocyte differentiation. In this study, we examined the impact of Cd on non-homologous end joining pathway by analyzing T cell development in the thymus of mice that received Cd-supplemented drinking water. In vivo, the absence of major alteration indicates that Cd does not affect NHEJ, despite its accumulation in the thymus. Cd contamination affects only a discrete population of developing thymocytes. However, these cells are functional as the cellular response observed in mice following gamma-radiation exposure is identical in treated and control mice. Furthermore, Cd diet did not perturb the redox status in thymocytes and more importantly did not generate significant DNA lesions in organs that accumulate the highest concentration of Cd. Our results show that in vivo, Cd does not affect NHEJ or base and nucleotide repair, and that Cd toxicity to T cells is rather linked to cell cycle perturbations.
Published: 2007
Full Text: View/download PDF

12. Oxidation of the sugar moiety of DNA by ionizing radiation or bleomycin could induce the formation of a cluster DNA lesion

Author: Benoit Duroux, Peggy Regulus, Jean Cadet, Pierre-Alain Bayle, Jean-Luc Ravanat, Alain Favier, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), UMR 8124 Laboratoire de Chimie Bioorganique et Bioinorganique, Université Paris Sud (Paris 11), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Models, Molecular, DNA damage, Bleomycin, Adduct, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Radiation, Ionizing, Animals, Carcinogen, 030304 developmental biology, 0303 health sciences, Multidisciplinary, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Deoxyribose, DNA, Biological Sciences, DNA extraction, 3. Good health, chemistry, Biochemistry, 030220 oncology & carcinogenesis, Nucleic Acid Conformation, Cattle, Cytosine, DNA Damage
Abstract: Bleomycin, a radiomimetic drug currently used in human cancer therapy, is a well known carcinogen. Its toxicity is mostly attributed to its potentiality to induce DNA double strand breaks likely arising from the formation of two vicinal DNA strand breaks, initiated by C4-hydrogen abstraction on the 2-deoxyribose moiety. In this work we demonstrate that such a hydrogen abstraction reaction is able to induce the formation of a clustered DNA lesion, involving a 3′ strand break together with a modified sugar residue exhibiting a reactive α,β-unsaturated aldehyde that further reacts with a proximate cytosine base. The lesion thus produced was detected as a mixture of four isomers by HPLC coupled to tandem mass spectrometry subsequent to DNA extraction and enzymatic digestion. The modified nucleosides that constitute new types of cytosine adducts were identified as the likely two pairs of diastereomers of 6-(2-deoxy-β- d - erythro -pentofuranosyl)-2-hydroxy-3(3-hydroxy-2-oxopropyl)-2,6-dihydroimidazo[1,2-c]-pyrimidin-5(3 H )-one as inferred from mass spectrometry and NMR analyses of the chemically synthesized nucleosides. We demonstrate that bleomycin, and to a minor extent ionizing radiation, are able to induce significant amounts of the cytosine damage in cellular DNA. In addition, the repair kinetic of the lesion in a human lymphocyte cell line is rather slow, with a half-life of 10 h. The 2′-deoxycytidine adducts thus characterized that represent the first example of complex DNA lesions isolated and identified in cellular DNA upon one radical hit are likely to play an important role in the toxicity of bleomycin.
Published: 2007
Full Text: View/download PDF

13. Analysis of Fluoroquinolone-mediated Photosensitization of 2′-Deoxyguanosine, Calf Thymus and Cellular DNA: Determination of Type-I, Type-II and Triplet-Triplet Energy Transfer Mechanism Contribution¶

Author: Jean Cadet, Jean-Luc Ravanat, Francette Odin, Thierry Douki, Sylvain Caillat, and Sylvie Sauvaigo
Subjects: Pyrimidine dimer, Thymus Gland, Photochemistry, Biochemistry, Cyclobutane, chemistry.chemical_compound, Anti-Infective Agents, medicine, Animals, Deoxyguanosine, Physical and Theoretical Chemistry, Norfloxacin, Photosensitizing Agents, DNA, General Medicine, Comet assay, Energy Transfer, chemistry, Cattle, Comet Assay, Ofloxacin, Phototoxicity, Fluoroquinolones, medicine.drug
Abstract: Fluoroquinolone (FQ) antibacterials are known to exhibit photosensitization properties leading to the formation of oxidative damage to DNA. In addition, photoexcited lomefloxacin (Lome) was recently shown to induce the formation of cyclobutane pyrimidine dimers via triplet-triplet energy transfer. The present study is aimed at gaining further insights into the photosensitization mechanisms of several FQ including enoxacin (Enox), Lome, norfloxacin (Norflo) and ofloxacin (Oflo). This was achieved by monitoring the formation of DNA base degradation products upon UVA-mediated photosensitization of 2'-deoxyguanosine, isolated and cellular DNA. Oflo and Norflo act mainly via a Type-II mechanism whereas Lome and, to a lesser extent, Enox behave more like Type-I photosensitizers. However, the extent of oxidative damage was found to be relatively low. In contrast, it was found that cyclobutane thymine dimers represent the major class of damage induced by Enox, Lome and Norflo within isolated and cellular DNA upon UVA irradiation. This striking observation confirms that FQ are able to promote efficient triplet energy transfer to DNA. The levels of photosensitized formation of strand breaks, alkali-labile sites and oxidative damage to cellular DNA, as measured by the comet assay, were confirmed to be rather low. Therefore, we propose that the phototoxic effects of FQ are mostly accounted for energy transfer mechanism rather than by Type-I or -II photosensitization processes.
Published: 2007
Full Text: View/download PDF

14. Gadolinium nanoparticles and contrast agent as radiation sensitizers

Author: Hélène Elleaume, Lucie Sancey, Thierry Brochard, Pascal Perriat, Marie Carrière, François Lux, Mélanie Flaender, Rolf F. Barth, Jean-Luc Ravanat, Florence Taupin, Josiane Arnaud, R. Delorme, Jean-François Mayol, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Modélisation et Simulation de Systèmes (LM2S), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Rayonnement synchrotron et Recherche Médicale, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut de Recherche Biomédicale des Armées (IRBA), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Ohio State University [Columbus] (OSU), Labex Primes (ANR-11-LABX-0063) of Lyon UniversityInvestissements d'Avenir (NR-11-IDEX-0007), ANR-10-BLAN-1532,RAPHAELO,Radiothérapie par Photo-Activation d'Eléments LOurds(2010), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Vernay, Emmanuelle, and BLANC - Radiothérapie par Photo-Activation d'Eléments LOurds - - RAPHAELO2010 - ANR-10-BLAN-1532 - BLANC - VALID
Subjects: Radiosensitizer, photoelectric effect, Radiation-Sensitizing Agents, BRAIN-TUMORS, [PHYS.NEXP] Physics [physics]/Nuclear Experiment [nucl-ex], Cell Survival, Gadolinium, chemistry.chemical_element, Nanoparticle, Contrast Media, Metal Nanoparticles, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, law.invention, [SDV.CAN] Life Sciences [q-bio]/Cancer, law, Cell Line, Tumor, Animals, Radiology, Nuclear Medicine and imaging, Irradiation, Clonogenic assay, DOSE-ENHANCEMENT, CLINICAL SCENARIO, RADIOSENSITIZATION, Photons, [PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Radiological and Ultrasound Technology, business.industry, Chemistry, X-Rays, Photoelectric effect, contrast agent, ADJUVANT TEMOZOLOMIDE, SYNCHROTRON STEREOTACTIC RADIOTHERAPY, Synchrotron, Rats, Colloidal gold, GOLD NANOPARTICLES, Biophysics, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], nanoparticles, SQUAMOUS-CELL CARCINOMA, MEGAVOLTAGE PHOTON BEAMS, Nuclear medicine, business
Abstract: International audience; The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist® in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV–80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL−1), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44 ± 0.33 and 1.50 ± 0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66 ± 0.17 and 1.01 ± 0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly 'energy dependent' for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs.
Published: 2015
Full Text: View/download PDF

15. Dpy19l2-deficient globozoospermic sperm display altered genome packaging and DNA damage that compromises the initiation of embryo development

Author: Sylviane Hennebicq, Raoudha Zouari, Sandra Yassine, Thomas Karaouzène, Catherine Metzler-Guillemain, Jessica Escoffier, Christophe Arnoult, Hoi Chang Lee, Guillaume Martinez, Rafael A. Fissore, Jean-Luc Ravanat, Pierre F. Ray, Charles Coutton, AGeing and IMagery (AGIM), Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), Centre Hospitalier Universitaire [Grenoble] (CHU), Clinique de Promotion des Sciences de la Reproduction - Les Jasmins (CPSR), Clinique de Promotion des Sciences de la Reproduction, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Massachusetts [Amherst] (UMass Amherst), University of Massachusetts System (UMASS), Laboratoire d’Aide à la Procréation, Département de Génétique et Procréation (CECOS), Hôpital Couple Enfant de Grenoble-CHU de Grenoble, CHU de Grenoble, UM GI-DPI, 38000, Grenoble, France., ANR-09-GENO-0013,ICG2I,Identification et Caractérisation de gènes impliqués dans l'infertilité.(2009), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Clinique de Promotion des Sciences de la Reproduction [Tunis] (CPSR), and Polyclinique les Jasmins [Tunis]
Subjects: Male, Embryology, Fluorescent Antibody Technique, Protamine, Intracytoplasmic Sperm, Mice, Mouse Oocytes, 0302 clinical medicine, Protamines, reproductive and urinary physiology, Genetics, Mice, Knockout, [PHYS]Physics [physics], 0303 health sciences, 030219 obstetrics & reproductive medicine, DNA compaction, Obstetrics and Gynecology, Embryo, Articles, Spermatids, Spermatozoa, Testicular sperm extraction, Cell biology, Chromatin, Female, Causes Infertility, DNA damage, Dpy19l2, Biology, 03 medical and health sciences, Animals, Humans, Male Infertility, Spermatogenesis, Molecular Biology, Globozoospermia, Infertility, Male, 030304 developmental biology, urogenital system, Membrane Proteins, Oocyte activation, Cell Biology, Sperm, Chromatin-Structure, Testicular Spermatozoa, Reproductive Medicine, Fertilization, biology.protein, Oocytes, Developmental Biology, DNA Damage
Abstract: International audience; We recently identified the DPY19L2 gene as the main genetic cause of human globozoospermia. Non-genetically characterized cases of globozoospermia were associated with DNA alterations, suggesting that DPY19L2-dependent globozoospermia maybe associated with poor DNA quality. However the origins of such defects have not yet been characterized and the consequences on the quality of embryos generated with globozoospermic sperm remain to be determined. Using the mouse model lacking Dpy19l2, we compared several key steps of nuclear compaction. We show that the kinetics of appearance and disappearance of the histone H4 acetylation waves and of transition proteins are defective. More importantly, the nuclear invasion by protamines does not occur. As a consequence, we showed that globozoospermic sperm presented with poor sperm chromatin compaction and sperm DNA integrity breakdown. We next assessed the developmental consequences of using such faulty sperm by performing ICSI. We showed in the companion article that oocyte activation (OA) with globozoospermic sperm is very poor and due to the absence of phospholipase C zeta; therefore artificial OA (AOA) was used to bypass defective OA. Herein, we evaluated the developmental potential of embryos generated by ICSI + AOA in mice. We demonstrate that although OA was fully rescued, preimplantation development was impaired when using globozoospermic sperm. In human, a small number of embryos could be generated with sperm from DPY19L2-deleted patients in the absence of AOA and these embryos also showed a poor developmental potential. In conclusion, we show that chromatin compaction during spermiogenesis in Dpy19l2 KO mouse is defective and leads to sperm DNA damage. Most of the DNA breaks were already present when the sperm reached the epididymis, indicating that they occurred inside the testis. This result thus suggests that testicular sperm extraction in Dpy19l2-dependent globozoospermia is not recommended. These defects may largely explain the poor embryonic development of most mouse and human embryos obtained with globozoospermic sperm.
Published: 2015
Full Text: View/download PDF

16. N6-Methyldeoxyadenosine, a nucleoside commonly found in prokaryotes, induces C2C12 myogenic differentiation

Author: Alain Favier, Didier Wion, Marie Pierre Charles, Jean Cadet, Danièle Adamski, François Berger, Jean-Luc Ravanat, Gabriella D'Orazi, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Spectrometry, Mass, Electrospray Ionization, Time Factors, Cellular differentiation, Blotting, Western, Cell Culture Techniques, Biophysics, Biology, Biochemistry, Cell Line, Mice, 03 medical and health sciences, chemistry.chemical_compound, Animals, Cell Lineage, Molecular Biology, Cells, Cultured, Chromatography, High Pressure Liquid, ComputingMilieux_MISCELLANEOUS, Myogenin, 030304 developmental biology, 0303 health sciences, Deoxyadenosines, Reverse Transcriptase Polymerase Chain Reaction, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Myogenesis, Adenine, 030302 biochemistry & molecular biology, Cell Differentiation, Nucleosides, DNA, Cell Biology, Molecular biology, chemistry, Prokaryotic DNA replication, Cell culture, Nucleoside, C2C12
Abstract: N(6)-methyl-2(')-deoxyadenosine (MedAdo) is a nucleoside naturally found in prokaryotic DNA. Interestingly, the N(6)-methylation of adenine in DNA seems to have been counter-selected during the course of evolution since MedAdo has not been detected in mammalian DNA until now. We show here that treatment with MedAdo induces myogenesis in C2C12 myoblasts. The presence of MedAdo in C2C12 DNA was investigated using a method based on HPLC coupled to electrospray ionization tandem mass spectrometry which is several thousand fold more sensitive than assays used previously. By this procedure, MedAdo is detected in the DNA from MedAdo-treated cells but remains undetectable in the DNA from control cells. Furthermore, MedAdo regulates the expression of p21, myogenin, mTOR, and MHC. Interestingly, in the pluripotent C2C12 cell line, MedAdo drives the differentiation towards myogenesis only. Thus, the biological effect of MedAdo is suppressed in the presence of BMP-2 which transdifferentiates C2C12 from myogenic into osteogenic lineage cells. Taken together these results point to MedAdo as a novel inducer of myogenesis and further extends the differentiation potentialities of this methylated nucleoside. Furthermore, these data raise the intriguing possibility that the biological effects of MedAdo on cell differentiation may have led to its counter-selection in eukaryotes.
Published: 2004
Full Text: View/download PDF

17. Radiation-Induced DNA Damage: Formation, Measurement, and Biochemical Features

Author: Sylvie Sauvaigo, Jean Cadet, Thierry Douki, Didier Gasparutto, Evelyne Muller, Jean-Pierre Pouget, Anthony Romieu, Sophie Bellon, Jean-Luc Ravanat, and Sandrine Frelon
Subjects: DNA Repair, Chemistry, DNA damage, DNA repair, Guanine, Health, Toxicology and Mutagenesis, Free radical damage to DNA, DNA, General Medicine, Toxicology, Molecular biology, Substrate Specificity, Pathology and Forensic Medicine, Thymine, Comet assay, chemistry.chemical_compound, DNA Repair Enzymes, Biochemistry, Gamma Rays, DNA glycosylase, Mutagenesis, Site-Directed, Animals, Humans, Radiation Induced DNA Damage, DNA Damage
Abstract: Most of the reactions induced by *OH radicals (indirect effects) and by one-electron oxidation (direct effects) as the result of exposure to ionizing radiation may be described for the four main DNA nucleobases. Relevant information is now available on the formation of single and tandem base lesions implicating guanine as the most susceptible DNA component to the deleterious effects of ionizing radiation. In contrast, there is still a paucity of information on the radiation-induced formation of base damage within cellular DNA. This is mostly a result of difficulties associated with the measurement of oxidized purine and pyrimidine bases that appear to be generated in very low yields. This is illustrated by the measurement of low amounts of E. coli formamidopyrimidine glycosylase- and endonuclease-III-sensitive sites in the DNA of neoplastic monocytes upon exposure to gamma rays (48 and 53 per 10(9) bases and per Gy, respectively) using a modified comet assay (the overall number of strand breaks and alkali-labile sites was estimated to be 130 per 10(9) bases and per Gy). More specifically, the level of several radiation-induced modified bases, including thymine glycols, 5-formyluracil, 5-(hydroxymethyl)uracil, 8-oxo-7,8-dihydroguanine, and 8-oxo-7,8-dihydroadenine, together with related formamidopyrimidine derivatives was assessed using the suitable HPLC-MS/MS method. Information is also provided on the substrate specificity of DNA repair enzymes and the mutagenic potential of base lesions using site-specific modified oligonucleotides as the probes.
Published: 2004
Full Text: View/download PDF

18. Exercise training combined with antioxidant supplementation prevents the antiproliferative activity of their single treatment in prostate cancer through inhibition of redox adaptation

Author: Françoise Rannou-Bekono, Amélie Rébillard, Luz Lefeuvre-Orfila, Arlette Gratas-Delamarche, Jean-Luc Ravanat, Jordan Gueritat, Sophie Vincent, Armel Crétual, Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes (UR)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire de Linguistique de Nantes (LLING), Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Institut National de la Recherche Agronomique (INRA)-IFR140, Détoxication et réparation tissulaire, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Antioxidant, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Administration, Oral, Physical exercise, medicine.disease_cause, Biochemistry, Antioxidants, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Physiology (medical), Internal medicine, Cell Line, Tumor, Physical Conditioning, Animal, TBARS, medicine, Animals, Extracellular Signal-Regulated MAP Kinases, Muscle, Skeletal, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Whole blood, Cell Proliferation, Lythraceae, 0303 health sciences, Kinase, Chemistry, Plant Extracts, Superoxide Dismutase, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Prostatic Neoplasms, 3. Good health, Rats, Tumor Burden, Oxidative Stress, Endocrinology, 030220 oncology & carcinogenesis, Fruit, Cancer cell, Disease Progression, Oxidation-Reduction, Oxidative stress, Neoplasm Transplantation
Abstract: In preclinical models, exercise training (ET) or pomegranate juice (PJ) prevents prostate cancer progression. Here, we hypothesized that physical exercise combined with antioxidants could induce synergistic effects through oxidative stress modulation. Forty male Copenhagen rats with prostate tumors were divided into four groups: control, PJ, ET, and PJ+ET. Rats from the PJ group consumed 750 µl of PJ daily, rats from the ET group ran on a treadmill 5 days per week, and PJ+ET rats received the combined treatment. Each week, tumor growth was evaluated. After 4 weeks of treatment, the rats were euthanized and blood, muscles, and tumors were collected. Tumor Ki67, extracellular signal-regulated kinase (ERK) activation, Bcl-2 expression, and enzymatic and nonenzymatic antioxidant defenses, as well as oxidative stress markers (oxidized base, lipid peroxidation, protein carbonylation), were measured. PJ or ET significantly decreased prostate tumor proliferation (Ki67 staining, p
Published: 2014
Full Text: View/download PDF

19. Oxidatively generated damage to cellular DNA by UVB and UVA radiation

Author: Jean Cadet, Thierry Douki, Jean-Luc Ravanat, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Faculté de médecine et des sciences de la santé [Sherbrooke] (UdeS), and Université de Sherbrooke (UdeS)
Subjects: Purine, One-Electron Oxidation, Carbonate, Guanine, DNA damage, Ultraviolet Rays, Free radical damage to DNA, Cyclobutane Pyrimidine, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Whole Human Skin, medicine, Animals, Humans, Physical and Theoretical Chemistry, Dimers, 030304 developmental biology, [PHYS]Physics [physics], 0303 health sciences, Nitric-Oxide Synthase, Singlet Oxygen, Superoxide, Radical-Anion, General Medicine, DNA, 0104 chemical sciences, Oxidative Stress, Narrow-Band UVB, chemistry, Double-Strand Breaks, Hydroxyl radical, Cultured Human Skin, Human Skin Cells, Oxidative stress
Abstract: International audience; This review article focuses on a critical survey of the main available information on the UVB and UVA oxidative reactions to cellular DNA as the result of direct interactions of UV photons, photosensitized pathways and biochemical responses including inflammation and bystander effects. UVA radiation appears to be much more efficient than UVB in inducing oxidatively generated damage to the bases and 2-deoxyribose moieties of DNA in isolated cells and skin. The UVA-induced generation of 8-oxo-7,8-dihydroguanine is mostly rationalized in terms of selective guanine oxidation by singlet oxygen generated through type II photosensitization mechanism. In addition, hydroxyl radical whose formation may be accounted for by metal-catalyzed Haber-Weiss reactions subsequent to the initial generation of superoxide anion radical contributes in a minor way to the DNA degradation. This leads to the formation of both oxidized purine and pyrimidine bases together with DNA single-strand breaks at the exclusion, however, of direct double-strand breaks. No evidence has been provided so far for the implication of delayed oxidative degradation pathways of cellular DNA. In that respect putative characteristic UVA-induced DNA damage could include single and more complex lesions arising from one-electron oxidation of the guanine base together with aldehyde adducts to amino-substituted nucleobases.
Published: 2014
Full Text: View/download PDF

20. DNA-Polyamine Cross-Links Generated upon One Electron Oxidation of DNA

Author: Marisa Taverna-Porro, Jean-Luc Ravanat, Laure Bobyk, Stéphanie Silerme, Camille Cuier, Christine Saint-Pierre, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Stereochemistry, Guanine, Electrospray ionization, Electrons, 010402 general chemistry, Toxicology, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Tandem Mass Spectrometry, Polyamines, Animals, Chromatography, High Pressure Liquid, 030304 developmental biology, 0303 health sciences, Nucleophilic addition, Molecular Structure, General Medicine, DNA, Combinatorial chemistry, 0104 chemical sciences, Spermidine, Cross-Linking Reagents, chemistry, Covalent bond, Putrescine, Cattle, Polyamine, Oxidation-Reduction, [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract: International audience; The possibility to induce the formation of covalent cross-links between polyamines and guanine following one electron oxidation of double stranded DNA has been evaluated. For such a purpose, a strategy has been developed to chemically synthesize the polyamine-C8-guanine adducts, and efforts have been made to characterize them. Then, an analytical method, based on HPLC separation coupled through electrospray ionization to tandem mass spectrometry, has been setup for their detection and quantification. Using such a sensitive approach, we have demonstrated that polyamine-C8-guanine adducts could be produced with significant yields in double stranded DNA following a one-electron oxidation reaction induced by photosensitization. These adducts, involving either putrescine, spermine, or spermidine, are generated by the nucleophilic addition of primary amino groups of polyamines onto the C8 position of the guanine radical cation. Our data demonstrate that such a nucleophilic addition of polyamines is much more efficient than the addition of a water molecule that leads to 8-oxo-7,8-dihydroguanine formation.
Published: 2014
Full Text: View/download PDF

21. Low Doses of Gamma-Irradiation Induce an Early Bystander Effect in Zebrafish Cells Which Is Sufficient to Radioprotect Cells

Author: Sandrine Pereira, Anne-Hélène Davin, Nicolas Foray, Véronique Malard, Christelle Adam-Guillermin, Jean Armengaud, Jean-Luc Ravanat, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie des Systèmes Perturbés (LBSP), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire Innovations technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'écotoxicologie des radionucléides (PRP-ENV/SERIS/LECO), European Project: 269672,EC:FP7:Fission,FP7-Fission-2010,STAR(2011), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire d'écotoxicologie des radionucléides (IRSN/PRP-ENV/SERIS/LECO), Service de Recherche et d'Expertise sur les Risques environnementaux (IRSN/PRP-ENV/SERIS), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Ravanat, Jean-Luc, and Strategy for Allied Radioecology - STAR - - EC:FP7:Fission2011-02-01 - 2015-07-31 - 269672 - VALID
Subjects: Proteomics, Radioprotection, Embryo, Nonmammalian, Time Factors, Micronuclei, Biochemistry, Epigenesis, Genetic, Histones, Nucleic Acids, Molecular Cell Biology, Medicine and Health Sciences, Bystander effect, DNA Breaks, Double-Stranded, Zebrafish, Genetics, Spectrometric Identification of Proteins, Radiation, Gamma Radiation, Multidisciplinary, DNA methylation, Radiology and Imaging, Physics, Adaptation, Physiological, Dose–response relationship, Physical Sciences, Micronucleus test, Medicine, Epigenetics, Research Article, DNA damage, DNA repair, Science, Radiation Biophysics, Biophysics, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Radiation Protection, Dosimetry, Animals, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Secretion, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Nuclear Physics, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Biology and life sciences, Ecology and Environmental Sciences, Gamma rays, Embryos, Radiobiology, Dose-Response Relationship, Radiation, DNA, Cell Biology, Bystander Effect, Zebrafish Proteins, Embryonic stem cell, Molecular biology, Kinetics, Bioindicators
Abstract: International audience; The term ''bystander effect'' is used to describe an effect in which cells that have not been exposed to radiation are affected by irradiated cells though various intracellular signaling mechanisms. In this study we analyzed the kinetics and mechanisms of bystander effect and radioadaptation in embryonic zebrafish cells (ZF4) exposed to chronic low dose of gamma rays. ZF4 cells were irradiated for 4 hours with total doses of gamma irradiation ranging from 0.01-0.1 Gy. In two experimental conditions, the transfer of irradiated cells or culture medium from irradiated cells results in the occurrence of DNA double strand breaks in non-irradiated cells (assessed by the number of c-H2AX foci) that are repaired at 24 hours post-irradiation whatever the dose. At low total irradiation doses the bystander effect observed does not affect DNA repair mechanisms in targeted and bystander cells. An increase in global methylation of ZF4 cells was observed in irradiated cells and bystander cells compared to control cells. We observed that pre-irradiated cells which are then irradiated for a second time with the same doses contained significantly less c-H2AX foci than in 24 h gamma-irradiated control cells. We also showed that bystander cells that have been in contact with the pre-irradiated cells and then irradiated alone present less c-H2AX foci compared to the control cells. This radioadaptation effect is significantly more pronounced at the highest doses. To determine the factors involved in the early events of the bystander effect, we performed an extensive comparative proteomic study of the ZF4 secretomes upon irradiation. In the experimental conditions assayed here, we showed that the early events of bystander effect are probably not due to the secretion of specific proteins neither the oxidation of these secreted proteins. These results suggest that early bystander effect may be due probably to a combination of multiple factors.
Published: 2014
Full Text: View/download PDF

22. Repair and Mutagenic Potential of Oxaluric Acid, a Major Product of Singlet Oxygen-Mediated Oxidation of 8-Oxo-7,8-dihydroguanine

Author: Duarte, Jean-Luc Ravanat, Michel Jaquinod, Didier Gasparutto, and Jean Cadet
Subjects: Guanine, DNA Repair, Free Radicals, DNA repair, Oligonucleotides, Oxidative phosphorylation, Toxicology, Substrate Specificity, Nucleobase, Deoxyribonuclease (Pyrimidine Dimer), chemistry.chemical_compound, Animals, Taq Polymerase, Nucleotide, DNA Polymerase beta, chemistry.chemical_classification, Oxamic Acid, Endodeoxyribonucleases, DNA synthesis, Singlet oxygen, Escherichia coli Proteins, DNA, General Medicine, DNA Polymerase I, Kinetics, chemistry, Biochemistry, Mutagenesis, Cattle, Reactive Oxygen Species, Oxidation-Reduction, DNA Damage
Abstract: Oxidative reactions within DNA commonly result in base modifications. Among the four DNA bases, guanine is the most susceptible to various oxidants, and its related oxidized form, 8-oxo-7,8-dihydroguanine, has been extensively studied in terms of repair and mutagenicity. However, 8-oxo-7,8-dihydroguanine is readily subjected to further oxidation, and this has become a point of interest. We recently found that singlet oxygen oxidation of 8-oxo-7,8-dihydroguanine led to the predominant formation of oxaluric acid as the final product. We report herein on the biological features of oxaluric acid dealing with in vitro DNA synthesis and its removal from DNA by repair enzymes. Nucleotide insertion opposite oxaluric acid, catalyzed by Kf exo(-) and Taq indicates, that oxaluric acid induces G to T and G to C transversions. On the other hand, oxaluric acid represents a block when synthesis is performed with pol beta. Interestingly, DNA repair experiments carried out with formamidopyrimidine DNA N-glycosylase (Fpg) and endonuclease III (endo III) show that oxaluric acid is a substrate for both enzymes. Values of k(cat)/K(m) for the Fpg-mediated removal of oxidative guanine lesions revealed that 8-oxoGua is only a slightly better substrate than oxaluric acid. Interestingly, the results obtained with endo III suggest that oxaluric acid is a much better substrate than is 5-hydroxycytosine (5-OHC), an oxidized pyrimidine base.
Published: 2000
Full Text: View/download PDF

23. Detection of 8-Oxoguanine in Cellular DNA Using 2,6-Diamino-8-oxopurine as an Internal Standard for High-Performance Liquid Chromatography with Electrochemical Detection

Author: Jovanka Markovic, Jean-Luc Ravanat, Eric Gremaud, Robert J. Turesky, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Male, Nitrilotriacetic Acid, Guanine, Colon, Formic acid, Biophysics, Kidney, Ferric Compounds, Biochemistry, High-performance liquid chromatography, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, Hydrolysis, 0302 clinical medicine, Electrochemistry, Animals, Deoxyguanosine, 2-Aminopurine, Molecular Biology, Chromatography, High Pressure Liquid, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Chromatography, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Nitrilotriacetic acid, Kidney metabolism, DNA, Cell Biology, 8-Oxoguanine, Rats, Liver, chemistry, Organ Specificity, 030220 oncology & carcinogenesis, Artifacts, Oxidation-Reduction
Abstract: The quantitative aspect of the electrochemical detection method to detect 8-oxo-7,8-dihydroguanine (8-oxoGua) has been improved by using an internal standard. In addition, emphasis was placed on the reduction of artifactual oxidation of DNA during isolation and hydrolysis. Nuclear DNA was isolated from rat organs and purified on an anion-exchange column following treatment with proteinase K and RNase. DNA hydrolysis to nucleobases or nucleosides was performed using either formic acid treatment or enzymatic digestion, respectively. The levels of either 8-oxoGua or 8-hydroxy-7,8-dihydro-2'-deoxyguanosine were comparable. For accurate quantification, 2,6-diamino-8-oxopurine [(NH2)2-OH-Pur], added prior to hydrolysis, was used as an internal standard for the high-performance liquid chromatography with electrochemical detection assay. The baseline level of 8-oxoGua in DNA of Sprague-Dawley rats was estimated to be 2 to 5 8-oxoGua residues per 10(6) DNA bases, with slight differences depending on the tissue origin. In agreement with the results of previous observations, the level of the oxidized base in the kidney of animal treated with iron complexed to nitrilotriacetic acid (Fe-NTA) (15 mg/kg) was three- to fourfold higher than that of untreated rats or animals treated with a saline solution, while there was no change in 8-oxoGua levels in the liver and colon of these treated animals.
Published: 1998
Full Text: View/download PDF

24. Photoactivation of gold nanoparticles for glioma treatment

Author: Karin Pernet-Gallay, Jean-Luc Ravanat, M. Edouard, M. Vautrin, Laure Bobyk, Hélène Elleaume, Pierre Deman, Julie Delaroche, Jean-François Adam, François Estève, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biomedical Beamline (ID17), European Synchrotron Radiation Facility (ESRF), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), and Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Materials science, Light, Cell Survival, Biomedical Engineering, Pharmaceutical Science, Medicine (miscellaneous), Metal Nanoparticles, Bioengineering, Nanotechnology, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, In vivo, Glioma, Cell Line, Tumor, medicine, Animals, General Materials Science, Clonogenic assay, F98 glioma, Brain Neoplasms, Drug Administration Routes, X-Rays, Brain, medicine.disease, In vitro, Rats, Inbred F344, 3. Good health, Rats, Neostriatum, Radiography, Colloidal gold, 030220 oncology & carcinogenesis, Toxicity, Cancer research, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Molecular Medicine, Gold, Subcellular Fractions
Abstract: Radiosensitization efficacy of gold nanoparticles (AuNPs) with low energy radiations (88keV) was evaluated in vitro and in vivo on rats bearing glioma. In vitro, a significant dose-enhancement factor was measured by clonogenic assays after irradiation with synchrotron radiation of F98 glioma cells in presence of AuNPs (1.9 and 15nm in diameter). In vivo, 1.9nm nanoparticles were found to be toxic following intracerebral delivery in rats bearing glioma, whether no toxicity was observed using 15nm nanoparticles at the same concentration (50mg/mL). The therapeutic efficacy of gold photoactivation was determined by irradiating the animals after intracerebral infusion of AuNPs. Survival of rats that had received the combination of treatments (AuNPs: 50mg/mL, 15Gy) was significantly increased in comparison with the survival of rats that had received irradiation alone. In conclusion, this experimental approach is promising and further studies are foreseen for improving its therapeutic efficacy. From the Clinical Editor These investigators report that gold nanoparticles of the correct size can be used to enhance the effects of irradiation in the context of a glioma model. Since many of the glioma varieties are currently incurable, this or similar approaches may find their way to clinical trials in the near future.
Published: 2013
Full Text: View/download PDF

25. Targeted and Off-Target (Bystander and Abscopal) Effects of Radiation Therapy: Redox Mechanisms and Risk/Benefit Analysis

Author: Jean-Pierre Pouget, Jean-Luc Ravanat, Alexandros G. Georgakilas, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), National Technical University of Athens [Athens] (NTUA), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used(2010), ANR-11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: musculoskeletal diseases, 0301 basic medicine, Free Radicals, Physiology, medicine.medical_treatment, Clinical Biochemistry, Biochemistry, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Comprehensive Invited Review, targeted effects, bystander effects, Neoplasms, Bystander effect, Medicine, Animals, Humans, [CHIM]Chemical Sciences, skin and connective tissue diseases, Molecular Biology, radiotherapy, General Environmental Science, business.industry, radionuclide therapy, Cell Biology, bacterial infections and mycoses, abscopal effects, humanities, 3. Good health, Radiation therapy, 030104 developmental biology, 030220 oncology & carcinogenesis, Risk-benefit analysis, Radionuclide therapy, Cancer research, General Earth and Planetary Sciences, nontargeted effects, business, Reactive Oxygen Species, Oxidation-Reduction
Abstract: International audience; Significance: Radiation therapy (from external beams to unsealed and sealed radionuclide sources) takes advantage of the detrimental effects of the clustered production of radicals and reactive oxygen species (ROS). Research has mainly focused on the interaction of radiation with water, which is the major constituent of living beings, and with nuclear DNA, which contains the genetic information. This led to the so-called target theory according to which cells have to be hit by ionizing particles to elicit an important biological response, including cell death. In cancer therapy, the Poisson law and linear quadratic mathematical models have been used to describe the probability of hits per cell as a function of the radiation dose. Recent Advances: However, in the last 20 years, many studies have shown that radiation generates ''danger'' signals that propagate from irradiated to nonirradiated cells, leading to bystander and other off-target effects. Critical Issues: Like for targeted effects, redox mechanisms play a key role also in off-target effects through transmission of ROS and reactive nitrogen species (RNS), and also of cytokines, ATP, and extracellular DNA. Particularly, nuclear factor kappa B is essential for triggering self-sustained production of ROS and RNS, thus making the bystander response similar to inflammation. In some therapeutic cases, this phenomenon is associated with recruitment of immune cells that are involved in distant irradiation effects (called ''away-from-target'' i.e., abscopal effects). Future Directions: Determining the contribution of targeted and off-target effects in the clinic is still challenging. This has important consequences not only in radiotherapy but also possibly in diagnostic procedures and in radiation protection. Antioxid. Redox Signal. 00, 000–000.
Published: 2012
Full Text: View/download PDF

26. Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions

Author: Jean Cadet, Stéphane Mouret, Thierry Douki, Jean-Luc Ravanat, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Keratinocytes, DNA Repair, Pyrimidine, Ultraviolet Rays, DNA damage, Stereochemistry, Pyrimidine dimer, Human skin, CHO Cells, 010402 general chemistry, Photochemistry, medicine.disease_cause, 01 natural sciences, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Cricetinae, medicine, Animals, Humans, Pyrimidone, Physical and Theoretical Chemistry, Skin, 030304 developmental biology, 0303 health sciences, Photosensitizing Agents, DNA, General Medicine, 0104 chemical sciences, chemistry, Pyrimidine Dimers, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Sunlight, sense organs, Oxidation-Reduction, Isomerization, Genotoxicity, DNA Damage
Abstract: International audience; The survey focuses on recent aspects of photochemical reactions to cellular DNA that are implicated through the predominant formation of mostly bipyrimidine photoproducts in deleterious effects of human exposure to sunlight. Recent developments in analytical methods have allowed accurate and quantitative measurements of the main DNA photoproducts in cells and human skin. Highly mutagenic CC and CT bipyrimidine photoproducts, including cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) are generated in low yields with respect to TT and TC photoproducts. Another striking finding deals with the formation of Dewar valence isomers, the third class of bipyrimidine photoproducts that is accounted for by UVA-mediated isomerization of initially UVB generated 6-4PPs. Cyclobutadithymine (T <> T) has been unambiguously shown to be involved in the genotoxicity of UVA radiation. Thus, T <> T is formed in UVA-irradiated cellular DNA according to a direct excitation mechanism with a higher efficiency than oxidatively generated DNA damage that arises mostly through the Type II photosensitization mechanism. C <> C and C <> T are repaired at rates intermediate between those of T <> T and 6-4TT. Evidence has been also provided for the occurrence of photosensitized reactions mediated by exogenous agents that act either in an independent way or through photodynamic effects.
Published: 2012
Full Text: View/download PDF

27. Chromatographic methods for the analysis of oxidatively damaged DNA

Author: Jean-Luc Ravanat, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: 0303 health sciences, Chromatography, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010401 analytical chemistry, Deoxyguanosine, General Medicine, DNA, 01 natural sciences, Biochemistry, 0104 chemical sciences, Review article, Oxidative damage, 03 medical and health sciences, 8-Hydroxy-2'-Deoxyguanosine, Animals, Humans, Oxidation-Reduction, ComputingMilieux_MISCELLANEOUS, Chromatography, High Pressure Liquid, 030304 developmental biology, DNA Damage
Abstract: Emphasis is placed in that review article on a detailed description of the different chromatographic analytical methods that were developed for measuring cellular levels of oxidatively generated DNA lesions. The different methods are critically reviewed taking into account the advantages and limitations of the assays. Particular attention is focused on possible causes of over- or underestimation that may explain at least partly the wide range of cellular levels of lesions and in particular 8-oxo-7,8-dihydro-2′-deoxyguanosine reported in the literature. In that respect a chronological presentation of the main significant developments is provided and appears to be of particular interest to follow the technical and methodological improvements performed over the years. Finally, future possible progresses in terms of both specificity and sensitivity are presented.
Published: 2011
Full Text: View/download PDF

28. Oxidative Stress, Inflammation, and DNA Damage in Rats after Intratracheal Instillation or Oral Exposure to Ambient Air and Wood Smoke Particulate Matter

Author: Nicklas Raun Jacobsen, Keld Alstrup Jensen, Steffen Loft, Pernille Høgh Danielsen, Peter Møller, Håkan Wallin, Jean-Luc Ravanat, Herman Autrup, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Male, Chemokine CXCL2, Administration, Oral, Gene Expression, Cell Count, 010501 environmental sciences, Toxicology, medicine.disease_cause, 01 natural sciences, DNA Glycosylases, chemistry.chemical_compound, DNA Adducts, Smoke, Ingestion, Deoxyguanosine, Chemokine CCL2, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Inhalation, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Wood, 3. Good health, Cytokines, Bronchoalveolar Lavage Fluid, medicine.medical_specialty, DNA damage, Proinflammatory cytokine, 03 medical and health sciences, Internal medicine, medicine, Intubation, Intratracheal, Animals, 030304 developmental biology, 0105 earth and related environmental sciences, Membrane Proteins, Pneumonia, Rats, Inbred F344, Rats, Oxidative Stress, Endocrinology, chemistry, 13. Climate action, Particulate Matter, Oxidative stress, Genotoxicity, Biomarkers, Heme Oxygenase-1, DNA Damage
Abstract: Wood combustion is a significant source of ambient particulate matter (PM) in many regions of the world. Exposure occurs through inhalation or ingestion after deposition of wood smoke particulate matter (WSPM) on crops and food. We investigated effects of ambient PM and WSPM by intragastric or intratracheal exposure in terms of oxidative stress, inflammation, genotoxicity, and DNA repair after 24 h in liver and lung tissue of rats. Rats were exposed to WSPM from high or low oxygen combustion and ambient PM collected in areas with and without many operating wood stoves or carbon black (CB) at the dose of 0.64 mg/kg body weight. The levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine, 1,N(6)-etheno-2'-deoxyadenosine, and 1-N(2)-etheno-2'-deoxyguanosine (εdG) were significantly increased with 23% (95% confidence interval [CI]: 0.1-45%), 54% (95% CI:18-90%), and 73% (95% CI: 31-134%) in the liver of rats exposed orally to CB, respectively. Rats orally exposed to PM from the wood stove area and low oxygen combustion WSPM (LOWS) had 35% (95% CI: 0.1-71%) and 45% (95% CI: 10-82%) increased levels of εdG in the liver, respectively. No significant differences were observed for bulky DNA adducts. Increased gene expression of proinflammatory cytokines, heme oxygenase-1, and oxoguanine DNA glycosylase 1 was observed in the liver following intragastric exposure and in the lung following instillation in particular of LOWS. Exposure to LOWS also increased the proportion of neutrophils in BAL fluid. These results indicate that WSPM and CB exert the strongest effect in terms of oxidative stress-induced response, inflammation, and genotoxicity in the organ closest to the port of entry.
Published: 2010
Full Text: View/download PDF

29. Evaluation of DNA Adducts, DNA and RNA Oxidative Lesions, and 3-Hydroxybenzo( a )pyrene as Biomarkers of DNA Damage in Lung Following Intravenous Injection of the Parent Compound in Rats

Author: Caroline Marie-Desvergne, Claude Viau, Jean-Luc Ravanat, Michèle Bouchard, Anne Maitre, NanoSafety Platform (NPS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), EPSP, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble, Centre Hospitalier Universitaire [Grenoble] (CHU), D épartement de sant é environnementale et santé au travail (IRSPUM), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-CHU Grenoble
Subjects: Male, Time Factors, DNA damage, Urinary system, [SDV]Life Sciences [q-bio], 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide, Urine, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 010501 environmental sciences, Toxicology, 01 natural sciences, Rats, Sprague-Dawley, DNA Adducts, 03 medical and health sciences, chemistry.chemical_compound, Tandem Mass Spectrometry, DNA adduct, Benzo(a)pyrene, polycyclic compounds, medicine, Animals, Deoxyguanosine, Benzopyrenes, Lung, Chromatography, High Pressure Liquid, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, 8-Hydroxy-2'-deoxyguanosine, DNA, General Medicine, Molecular biology, Rats, 3. Good health, medicine.anatomical_structure, Liver, Biochemistry, chemistry, 8-Hydroxy-2'-Deoxyguanosine, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Injections, Intravenous, RNA, Biomarkers, DNA Damage
Abstract: Biomarkers of exposure and effect were assessed in 40 male Sprague-Dawley rats injected intravenously with 40 micromol/kg of benzo(a)pyrene (BaP) to determine which biomarkers are more representative of BaP-induced DNA damage in lung. Lung, liver, blood, and urine were collected at t = 2, 4, 8, 16, 24, 33, 48, 72, and 360 h postdosing. Specific BaP-diol epoxide (BPDE)-DNA adducts, 8-hydroxy-7,8-dihydro-2'-deoxyguanosine (8-OHdGuo), were measured in lung, liver, and mononucleated blood cells by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Urinary 8-OHdGuo and 8-hydroxy-7,8-dihydroguanosine (8-OHGuo) were also determined by HPLC-MS/MS, and urinary 3-hydroxybenzo(a)pyrene was measured by HPLC/fluorescence. Between 2 and 72 h postdosing, BPDE-DNA adducts were significantly increased in lung, liver, and mononucleated blood cells of BaP-treated rats as compared to controls, with the highest levels found in lung. 8-OHdGuo levels also increased in lung of BaP-treated rats with values reaching statistical significance at 2, 8, and 16 h postinjection. No influence of BaP treatment was found on 8-OHdGuo and 8-OHGuo urinary excretions. BPDE-DNA adducts in lung were strongly correlated to urinary 3-OHBaP (r = 0.936 and p < 0.001) and to a lesser extent to blood BPDE-DNA adducts (r = 0.636 and p < 0.001), the latter of which were correlated to each other (r = 0.573 and p = 0.002). Urinary 3-OHBaP and BPDE-DNA adducts in mononucleated blood cells appear as relevant biomarkers of BaP genotoxic exposure and are highly promising for health risk assessment in humans.
Published: 2010
Full Text: View/download PDF

30. HO$^\bullet$ radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

Author: Jean-Luc Ravanat, Frédéric Auvré, J. Pablo Radicella, François Bergeron, Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), ANR-09-PIRI-0022,TODNAL,Lésions oxydatives tandem de l'ADN, formation réparation et mutagénèse(2009), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Purine, DNA Repair, DNA repair, DNA damage, Stereochemistry, Free radical damage to DNA, In Vitro Techniques, 010402 general chemistry, Models, Biological, 01 natural sciences, DNA Glycosylases, 03 medical and health sciences, chemistry.chemical_compound, Deoxyadenosine, Animals, Deoxyguanosine, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Deoxyadenosines, Hydroxyl Radical, [CHIM.ORGA]Chemical Sciences/Organic chemistry, DNA, Base excision repair, Biological Sciences, 0104 chemical sciences, chemistry, 8-Hydroxy-2'-Deoxyguanosine, Gamma Rays, DNA glycosylase, Cattle, Oxidation-Reduction, DNA Damage
Abstract: Reaction of HO • radicals with double-stranded calf thymus DNA produces high levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and, to a minor extent, 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxodAdo). Formation of the hydroxylated purine lesions is explained by addition of HO • to the C8 position of the purine moiety. It has been reported that tandem lesions containing a formylamine residue neighboring 8-oxodGuo could be produced through addition of a transiently generated pyrimidine peroxyl radical onto the C8 of an adjacent purine base. Formation of such tandem lesions accounted for ≈10% of the total 8-oxodGuo. In the present work we show that addition of HO • onto the C8 of purine accounts for only ∼5% of the generated 8-oxodGuo. About 50% of the 8-hydroxylated purine lesions, including 8-oxodGuo and 8-oxodAdo, are involved in tandem damage and are produced by peroxyl addition onto the C8 of a vicinal purine base. In addition, the remaining 45% of the 8-oxodGuo are produced by an electron transfer reaction, providing an explanation for the higher yield of formation of 8-oxodGuo compared to 8-oxodAdo. Interestingly, we show that >40% of the 8-oxodGuo involved in tandem lesions is refractory to excision by DNA glycosylases. Altogether our results demonstrate that, subsequently to a single oxidation event, peroxidation reactions significantly increase the yield of formation of hydroxylated purine modifications, generating a high proportion of tandem lesions partly refractory to base excision repair.
Published: 2010
Full Text: View/download PDF

31. Radiation-induced formation of purine 5′,8-cyclonucleosides in isolated and cellular DNA: high stereospecificity and modulating effect of oxygen

Author: Jean Cadet, Chryssostomos Chatgilialoglu, Jean-Luc Ravanat, Fabien Boussicault, Nourreddine Belmadoui, Maurizio Guerra, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Models, Molecular, Purine, DNA Repair, Guanine, Stereochemistry, DNA damage, Molecular Conformation, Stereoisomerism, 010402 general chemistry, 01 natural sciences, Biochemistry, Monocytes, Substrate Specificity, 03 medical and health sciences, chemistry.chemical_compound, Stereospecificity, Animals, Humans, Physical and Theoretical Chemistry, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, TANDEM MASS-SPECTROMETRY, PERFORMANCE LIQUID-CHROMATOGRAPHY, NUCLEOTIDE EXCISION-REPAIR, RADICAL-INDUCED FORMATION, AQUEOUS-SOLUTION, XERODERMA-PIGMENTOSUM, OXIDATIVE DAMAGE, STRAND SCISSION, C5' RADICALS, BASE DAMAGE, 0303 health sciences, Hydroxyl Radical, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Diastereomer, Water, DNA, Purine Nucleosides, 0104 chemical sciences, Oxygen, chemistry, Cyclization, Gamma Rays, Intramolecular force, Cattle, Stereoselectivity, DNA Damage
Abstract: The present work is aimed at gaining conclusive mechanistic insights into the radiation-induced formation of the 5'R and 5'S diastereomers of both adenine and guanine 5',8-cyclo-2'-deoxyribonucleosides, with emphasis on the delineation of the inhibitory effect of O(2) in isolated and cellular DNA. The levels of purine 5',8-cyclo-2'-deoxyribonucleosides as assessed by HPLC-MS/MS were found to decrease steadily with the increase of O(2) concentration, the 5',8-cyclo-2'-deoxyguanosine being produced more efficiently than the 5',8-cyclo-2'-deoxyadenosine for low O(2) concentrations. A high stereoselectivity was observed in the intramolecular addition of the C5' radical to the C8 of the purine leading, after the creation of the C5'-C8 bond and a subsequent oxidation step, to the predominant formation of the 5'R diastereomer for both purine 5',8-cyclonucleosides. The reduced formation yield of the 4 tandem lesions in the presence of O(2) explains, at least partly, the low efficiency of radiation-induced yields of the purine 5',8-cyclo-2'-deoxyribonucleosides in cellular DNA, which are about two orders of magnitude lower than the previously reported data obtained from HPLC-MS analysis.
Published: 2010
Full Text: View/download PDF

32. Effect of dietary fat-soluble vitamins A and E and proanthocyanidin-rich extract from grape seeds on oxidative DNA damage in rats

Author: Jean-François Narbonne, Daniel Ribera, Jean-Luc Ravanat, Bénédicte Morin, Carine Badouard, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)
Subjects: Vitamin, Male, food.ingredient, Antioxidant, medicine.medical_treatment, Biology, Toxicology, medicine.disease_cause, Antioxidants, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, food, medicine, Leukocytes, Animals, Vitamin E, Proanthocyanidins, Food science, Vitamin A, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Grape Seed Extract, Plant Extracts, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Retinol, Deoxyguanosine, General Medicine, Vitamins, Micronutrient, Diet, Rats, Fat-Soluble Vitamin, chemistry, Biochemistry, 8-Hydroxy-2'-Deoxyguanosine, 030220 oncology & carcinogenesis, Grape seed extract, Oxidative stress, Food Science, DNA Damage
Abstract: This study reports the effect of the fat-soluble vitamin A or vitamin E and grape seed proanthocyanidin extract (GSPE) on oxidative DNA damage estimated by 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG) contents in urine and leukocyte of rats. Little is known about the antioxidant potency of dietary anthocyanidins and consequently, the aim of this study was to establish whether anthocyanidins could act as putative antioxidant micronutrients. Seven groups of male Sprague-Dawley rats were fed during 47 days with the following diets: a basic diet, two deficient vitamin A or E diets, two supplemented vitamin A or E diets and two supplemented diets enriched with two doses of grape seed proanthocyanidin extract. At the end of the diet intervention period, 24h, urine and blood were collected. The levels of 8-oxodG in leukocytes rats were significantly lower in the supplemented vitamin A, E and GSPE diet groups with respect to the control group. However, consumption of alpha-tocopherol, vitamin A or GSPE had no effect on the excretion of the oxidised nucleoside 8-oxodG. These results suggest that a vitamin E and A and GSPE enriched-diets have a protective effect on oxidative DNA damage limited to rat leukocytes.
Published: 2008
Full Text: View/download PDF

33. Preventive effect of zinc against cadmium-induced oxidative stress in the rat testis

Author: Jean-Luc Ravanat, Alain Favier, Hafedh Abdelmelek, Salem Amara, Thierry Douki, Khémais Ben Rhouma, Mohsen Sakly, Pascale Guiraud, Catherine Garrel, Laboratoire de Physiologie Animale, Faculté des Sciences de Bizerte [Université de Carthage], Université de Carthage - University of Carthage-Université de Carthage - University of Carthage, Unité de Biochimie Hormonale et Nutritionnelle, Biologie-Toxicologie-pharmacologie, Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire ORSOX, Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Douki, Thierry, Centre Hospitalier Universitaire de Grenoble, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, Gonad, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, chemistry.chemical_element, Zinc, 010501 environmental sciences, Biology, medicine.disease_cause, 01 natural sciences, Models, Biological, Antioxidants, 03 medical and health sciences, chemistry.chemical_compound, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Internal medicine, Malondialdehyde, Testis, medicine, Metallothionein, Animals, Testosterone, Spermatogenesis, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, Superoxide Dismutase, DNA, Sperm, Mitochondria, Rats, Oxygen, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Oxidative Stress, medicine.anatomical_structure, Endocrinology, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Animal Science and Zoology, Oxidative stress, Cadmium
Abstract: The aim of this study was to investigate the antioxidant role of zinc (Zn) in the Cd-exposed testes of Wistar rats. Subchronic exposure to Cd (CdCl2, 40 mg/l, per os) for 30 days resulted in a significant reduction in growth rate (-11%) and relative weights of testes (-36%) and seminal vesicles (-80%). Treated rats displayed a decrease in testicular and plasma testosterone levels, respectively (-70%, P
Published: 2008

34. Oxidatively generated damage to the guanine moiety of DNA: Mechanistic aspects and formation in cells

Author: Jean-Luc Ravanat, Jean Cadet, Thierry Douki, Douki, Thierry, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Guanine, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, DNA damage, Radical, Cells, Context (language use), Electrons, 010402 general chemistry, Photochemistry, 01 natural sciences, Redox, 03 medical and health sciences, chemistry.chemical_compound, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Animals, Humans, 030304 developmental biology, 0303 health sciences, Singlet oxygen, General Medicine, General Chemistry, DNA, 0104 chemical sciences, [SDV.TOX] Life Sciences [q-bio]/Toxicology, chemistry, Biochemistry, 13. Climate action, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Hydroxyl radical, Oxidation-Reduction, DNA Damage
Abstract: Nuclear DNA and other molecules in living systems are continuously exposed to endogenously generated oxygen species. Such species range from the unreactive superoxide radical (O2*-)the precursor of hydrogen peroxide (H2O2)to the highly reactive hydroxyl radical (*OH). Exogenous chemical and physical agents, such as ionizing radiation and the UVA component of solar light, can also oxidatively damage both the bases and the 2-deoxyribose moieties of cellular DNA. Over the last two decades, researchers have made major progress in understanding the oxidation degradation pathways of DNA that are most likely to occur from either oxidative metabolism or exposure to various exogenous agents. In the first part of this Account, we describe the mechanistic features of one-electron oxidation reactions of the guanine base in isolated DNA and related model compounds. These reactions illustrate the complexity of the various degradation pathways involved. Then, we briefly survey the analytical methods that can detect low amounts of oxidized bases and nucleosides in cells as they are formed. Recent data on the formation of oxidized guanine residues in cellular DNA following exposure to UVA light, ionizing radiation, and high-intensity UV pulses are also provided. We discuss these chemical reactions in the context of *OH radical, singlet oxygen, and two-quantum photoionization processes.
Published: 2008

35. Undetectable levels of N6-methyl adenine in mouse DNA: Cloning and analysis of PRED28, a gene coding for a putative mammalian DNA adenine methyltransferase

Author: David Ratel, Lionel Breuillaud, Joël Lunardi, Marie-Pierre Charles, Jean-Luc Ravanat, Nadine Platet, François Berger, Didier Wion, Neurosciences précliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Fondation Jérôme Lejeune, Ligue Nationale contre le Cancer., and Issartel, Jean-Paul
Subjects: Site-Specific DNA-Methyltransferase (Adenine-Specific), Methyltransferase, Down syndrome, Biochemistry, Genome, adenine methylation, law.invention, Mice, chemistry.chemical_compound, Structural Biology, law, MESH: Animals, Cloning, Molecular, 0303 health sciences, DNA methylation, MESH: Alternative Splicing, 030302 biochemistry & molecular biology, Mitochondria, 3. Good health, Recombinant DNA, MESH: Adenine, MESH: Mitochondria, Biophysics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Molecular cloning, DNA, Mitochondrial, MESH: Site-Specific DNA-Methyltransferase (Adenine-Specific), 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Genetics, Animals, MESH: Cloning, Molecular, MESH: Genome, Molecular Biology, Gene, MESH: Mice, 030304 developmental biology, Adenine, N6-methyladenine, MESH: DNA, Mitochondrial, RNA, Cell Biology, Molecular biology, Alternative Splicing, chemistry, DNA
Abstract: International audience; Three methylated bases, 5-methylcytosine, N4-methylcytosine and N6-methyladenine (m6A), can be found in DNA. However, to date, only 5-methylcytosine has been detected in mammalian genomes. To reinvestigate the presence of m6A in mammalian DNA, we used a highly sensitive method capable of detecting one N6-methyldeoxyadenosine per million nucleosides. Our results suggest that the total mouse genome contains, if any, less than 10(3) m6A. Experiments were next performed on PRED28, a putative mammalian N6-DNA methyltransferase. The murine PRED28 encodes two alternatively spliced RNA. However, although recombinant PRED28 proteins are found in the nucleus, no evidence for an adenine-methyltransferase activity was detected.
Published: 2006
Full Text: View/download PDF

36. N6-methyladenine: the other methylated base of DNA

Author: Didier Wion, François Berger, Jean-Luc Ravanat, David Ratel, Neurosciences précliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), and Issartel, Jean-Paul
Subjects: MESH: Adenine, DNA repair, Eukaryotic DNA replication, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Eukaryotic Cells, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, chemistry.chemical_compound, MESH: DNA Methylation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Extrachromosomal DNA, Animals, MESH: Animals, 5-methylcytosine, MESH: Phylogeny, Phylogeny, 030304 developmental biology, Genetics, 0303 health sciences, DNA methylation, epigenetics, Circular bacterial chromosome, Adenine, 030302 biochemistry & molecular biology, DNA replication, N6-methyladenine, MESH: DNA, DNA, Eukaryotic Cells, chemistry, DNA supercoil
Abstract: DNA methylation is an epigenetic mechanism involved in many biological functions in prokaryotes and eukaryotes. Contrary to mammalian DNA, which is thought to contain only 5-methylcytosine (m5C), bacterial DNA contains two additional methylated bases, namely N6-methyladenine (m6A), and a more recently discovered minor base N4-methylcytosine (m4C). These modified bases are involved in the protection of bacterial DNA from the action of specific endonucleases via the host-specific restriction-modification system which is regarded as a defense mechanism against bacteriophage infection. However, if the main function of m5C and m4C in bacteria is the protection against restriction enzymes, the roles of m6A are multiple and include for example the regulation of virulence and the control of many bacterial DNA functions such as the replication, repair, expression and transposition of DNA. Hence, in regard to the multiple roles of m6A in bacteria, and to the well known tendency for m5C to deaminate in thymine, the selection of the mutagenic m5C instead of m6A in mammals as the only methylated base may seem surprising. However, even if adenine methylation is usually considered as a bacterial DNA feature, the presence of m6A is not restricted to prokaryotic DNA since this methylated base has been found in protist and plant DNAs. Furthermore, indirect evidence suggests the presence of m6A in mammal DNA, raising the possibility that this base has remained undetected due to the low sensitivity of the analytical methods used. This points to the importance to consider m6A as the sixth element of DNA.
Published: 2006
Full Text: View/download PDF

37. Influence of static magnetic field on cadmium toxicity: Study of oxidative stress and DNA damage in rat tissues

Author: Mohsen Sakly, Jean-Luc Ravanat, Catherine Garrel, Salem Amara, Pascale Guiraud, Hafedh Abdelmelek, Alain Favier, Thierry Douki, Khémais Ben Rhouma, Laboratoire de Physiologie Animale, Faculté des Sciences de Bizerte [Université de Carthage], Université de Carthage - University of Carthage-Université de Carthage - University of Carthage, Unité de Biochimie Hormonale et Nutritionnelle, Biologie-Toxicologie-pharmacologie, Centre Hospitalier Universitaire de Grenoble, Laboratoire ORSOX, Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Douki, Thierry
Subjects: Male, Cadmium Poisoning, medicine.medical_specialty, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, Antioxidant, medicine.medical_treatment, chemistry.chemical_element, 010501 environmental sciences, medicine.disease_cause, 01 natural sciences, Biochemistry, Antioxidants, Cadmium poisoning, Inorganic Chemistry, Superoxide dismutase, Magnetics, 03 medical and health sciences, chemistry.chemical_compound, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Internal medicine, medicine, Animals, Rats, Wistar, 030304 developmental biology, 0105 earth and related environmental sciences, chemistry.chemical_classification, 0303 health sciences, Cadmium, biology, Glutathione peroxidase, Malondialdehyde, medicine.disease, 6. Clean water, Rats, 3. Good health, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Oxidative Stress, Endocrinology, chemistry, Catalase, [SDV.TOX]Life Sciences [q-bio]/Toxicology, biology.protein, Molecular Medicine, Oxidative stress, DNA Damage
Abstract: In the present study, we investigated the effect of co-exposure to static magnetic field (SMF) and cadmium (Cd) on the biochemical parameters, antioxidant enzymes activity and DNA damage in rat tissues. Animals were treated with cadmium (CdCl(2), 40mg/L, per os) in drinking water during 4 weeks. Cd treatment induced an increase of plasma lactate dehydrogenase (LDH) and transaminases levels. Moreover, Cd treatment increased malondialdehyde (MDA) and 8-oxodGuo levels in rat tissues. However, the antioxidant enzymes activity such as the glutathione peroxidase (GPx), catalase (CAT) and the superoxide dismutase (SOD) were decreased in liver and kidney, while we noted a huge increase of hepatic and renal cadmium content. Interestingly, the combined effect of SMF (128mT, 1h/day during 30 consecutive days) and Cd (40mg/L, per os) decreased the GPx and CAT activities in liver compared to cadmium treated group. However, the association between SMF and Cd failed to alter transaminases, MDA and 8-oxodGuo concentration. Cd treatment altered antioxidant enzymes and DNA in liver and kidney of rats. Moreover, SMF associated to Cd disrupt this antioxidant response in liver compared to Cd-treated rats.
Published: 2006

38. Effects of subchronic exposure to static magnetic field on testicular function in rats

Author: Alain Favier, Hafedh Abdelmelek, Pascale Guiraud, Thierry Douki, Catherine Garrel, Mohsen Sakly, Khémais Ben Rhouma, Jean-Luc Ravanat, Salem Amara, Laboratoire de Physiologie Animale, Faculté des Sciences de Bizerte [Université de Carthage], Université de Carthage - University of Carthage-Université de Carthage - University of Carthage, Unité de Biochimie Hormonale et Nutritionnelle, Biologie-Toxicologie-pharmacologie, Centre Hospitalier Universitaire de Grenoble, Laboratoire ORSOX, Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Douki, Thierry, Centre Hospitalier Universitaire [Grenoble] (CHU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Male, medicine.medical_specialty, Antioxidant, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, medicine.medical_treatment, medicine.disease_cause, Antioxidants, 03 medical and health sciences, Magnetics, 0302 clinical medicine, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Internal medicine, Testis, medicine, Animals, Testosterone, Rats, Wistar, Spermatogenesis, 030304 developmental biology, 0303 health sciences, Chemistry, Superoxide Dismutase, Deoxyguanosine, Radioimmunoassay, General Medicine, DNA oxidation, DNA, Rats, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Testicular function, Endocrinology, 8-Hydroxy-2'-Deoxyguanosine, 030220 oncology & carcinogenesis, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Spermatozoa motility, Oxidation-Reduction, Oxidative stress
Abstract: The aim of this study was to investigate the effect of static magnetic field (SMF) exposure on testicular function, antioxidant status and DNA oxidation in rats.Male adult rats were exposed to SMF (128 mT; 1 h/day for 30 days). After sacrifice, the epididymal sperm number was counted. Testosterone concentration in plasma and testis was measured by radioimmunoassay. MDA level and GPx, CAT and SOD activities were used as markers of oxidative stress in testis. The 8-oxo-dG level is measured by the HPLC-EC system.Subchronic exposure to SMF has no effect on epididymal sperm count, spermatozoa motility and genital organ weight. In contrast, SMF induces a decrease of testicular and plasmatic testosterone levels, respectively (1.48 +/- 0.56 vs. 4.66 +/- 0.51 ng/g, p0.05; 0.97 +/- 0.16 vs. 1.64 +/- 0.18 ng/mL, p0.05). Exposed rats displayed an increase of malondialdehyde (2.01 +/- 0.03 vs. 1.47 +/- 0.06 micromol/g protein, p0.05), metallothioneins (1.04 +/- 0.22 vs. 0.37 +/- 0.06 microg/g, p0.05) and 8-oxo-dG concentrations (3.38 +/- 0.30 vs. 2.36 +/- 0.28 8-oxo-dG/10(6) bases, p0.05) in the testis. In the gonad, SMF decreases the CAT (14.33 +/- 1.16 vs. 21.67 +/- 2.05 U/mg protein, p0.05), GPx (177.40 +/- 5.97 vs. 237.20 +/- 15.65 U/mg protein, p0.05) and mitochondrial Mn-SOD (2.95 +/- 0.10 vs. 3.53 +/- 0.29 U/mg protein, p0.05) activities. However, cytosolic CuZn-SOD activity is unaffected.Subchronic exposure to SMF failed to alter spermatogenesis in rat testis. In contrast, the same treatment decreased testosterone levels and induced DNA oxidation.
Published: 2006

39. Irradiation in presence of iodinated contrast agent results in radiosensitization of endothelial cells: consequences for computed tomography therapy

Author: Aurélie Joubert, Jacques Balosso, François Estève, Thierry Brochard, Nicolas Foray, Marie-Claude Biston, A. M. Charvet, Jean-Luc Ravanat, Caroline Boudou, Rayonnement Synchrotron et Recherche Medicale (RSRM), Université Joseph Fourier - Grenoble 1 (UJF)-European Synchrotron Radiation Facility (ESRF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Biomedical Beamline (ID17), European Synchrotron Radiation Facility (ESRF), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Collaboration, European Synchrotron Radiation Facility (ESRF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), and Serduc, Raphael
Subjects: Cancer Research, DNA Repair, Contrast Media, DNA-Activated Protein Kinase, Radiation Tolerance, 030218 nuclear medicine & medical imaging, chemistry.chemical_compound, 0302 clinical medicine, Iodinated contrast, Medicine, MESH: Animals, Chromatography, High Pressure Liquid, MESH: DNA Repair, Radiation, MESH: Radiation Tolerance, MESH: DNA, 3. Good health, DNA-Binding Proteins, MESH: Cattle, Oncology, 030220 oncology & carcinogenesis, MESH: Synchrotrons, MESH: Endothelium, Vascular, DNA repair, Iomeprol, chemistry.chemical_element, Absorption (skin), Iodinated Contrast Agent, Protein Serine-Threonine Kinases, Iodine, MESH: Iopamidol, MESH: Protein-Serine-Threonine Kinases, 03 medical and health sciences, MESH: Contrast Media, Animals, Radiology, Nuclear Medicine and imaging, Irradiation, Kinase activity, MESH: Chromatography, High Pressure Liquid, MESH: DNA Damage, business.industry, DNA, Iopamidol, chemistry, Cancer research, MESH: DNA-Activated Protein Kinase, Cattle, Endothelium, Vascular, business, Nuclear medicine, Synchrotrons, MESH: DNA-Binding Proteins, DNA Damage
Abstract: International audience; PURPOSE: To date, iodinated contrast agents (ICA) are commonly used in medical imaging to improve tumor visualization by attenuating scanners X-rays. However, some adverse reactions to ICAs are still reported, and their molecular origin remains unclear. In 1983, it was proposed to visualize and treat ICA-loaded tumors by using scanners as therapy machines to enhance X-rays absorption at the iodine atoms. Theoretically, such physical conditions are optimized at 50 keV and can be easily obtained with synchrotrons. METHODS AND MATERIALS: Here, we examined the molecular and cellular responses of mammalian endothelial cells to radiation in the presence of iomeprol, one of the most extensively used ICAs. RESULTS: Irradiation with X-rays at 50 keV in the presence of iomeprol produced a strong radiosensitization effect. The same conclusion was reached with a standard medical irradiator but to a lesser extent. While such treatment did not produce additional DNA double-strand breaks, we observed a dose-dependent production of iodides due to the iomeprol radiolysis that inhibit double-strand break repair rate by decreasing DNA-PK kinase activity. CONCLUSIONS: Our data suggest that the concomitant use of ICA and radiation may be toxic when radiation-produced iodide concentrations and double-strand break yields are sufficient. The potential toxicity of ICAs during X-rays for diagnosis and therapy is discussed.
Published: 2005
Full Text: View/download PDF

40. Singlet oxygen-mediated damage to cellular DNA determined by the comet assay associated with DNA repair enzymes

Author: Jean Cadet, A. Favier, Jean-Luc Ravanat, Glaucia Regina Martinez, P. Di Mascio, Marisa Helena Gennari de Medeiros, Sylvie Sauvaigo, Sylvain Caillat, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)
Subjects: DNA repair, DNA damage, Clinical Biochemistry, 010402 general chemistry, 01 natural sciences, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Animals, Purine metabolism, Molecular Biology, 030304 developmental biology, 0303 health sciences, Singlet Oxygen, Singlet oxygen, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Thermal decomposition, 0104 chemical sciences, Comet assay, Membrane, DNA Repair Enzymes, chemistry, DNA-Formamidopyrimidine Glycosylase, Comet Assay, DNA, DNA Damage
Abstract: The damage profile produced by the reaction of singlet molecular oxygen with cellular DNA was determined using the comet assay associated with DNA repair enzymes. Singlet oxygen was produced intracellularly by thermal decomposition of a watersoluble endoperoxide of a naphthalene derivative which is able to penetrate through the membrane into mammalian cells. We found that the DNA modifications produced by singlet oxygen were almost exclusively oxidised purines recognised by the formamidopyrimidine DNA N-glycosylase. In contrast, significant amounts of direct strand breaks and alkalilabile sites or oxidised pyrimidines, detectable by the bacterial endonuclease III, were not produced.
Published: 2004
Full Text: View/download PDF

41. Riboflavin and UV-Light Based Pathogen Reduction: Extent and Consequence of DNA Damage at the Molecular Level

Author: Christopher B. Martin, Raymond P. Goodrich, Jean-Luc Ravanat, Jean Cadet, Patrick H. Ruane, Shawn D. Keil, Matthew S. Platz, Vijay Pochampalli Kumar, Owen Lockerbie, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Ultraviolet Rays, DNA damage, Guanine, Riboflavin, 030204 cardiovascular system & hematology, medicine.disease_cause, Jurkat cells, Biochemistry, Jurkat Cells, chemistry.chemical_compound, Tissue culture, 03 medical and health sciences, 0302 clinical medicine, Escherichia coli, Leukocytes, medicine, Animals, Humans, Physical and Theoretical Chemistry, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, DNA, General Medicine, Lambda phage, biology.organism_classification, Molecular biology, chemistry, 030221 ophthalmology & optometry, Cattle, Bacteria, DNA Damage
Abstract: We are developing a technology based on the combined application of riboflavin (RB) and light for inactivating pathogens in blood products while retaining the biological functions of the treated cells and proteins. Virus and bacteria reduction measured by tissue culture infectivity or colony formation with UV light alone and in combination with RB yield equivalent results. The effects of RB as a sensitizing agent on DNA in white cells, bacteria and viruses in combination with UV light exposure have been evaluated. UV-mediated DNA degradation in Jurkat T cells and leukocytes in plasma as measured by the FlowTACS assay was significantly increased in the presence of RB. Agarose gel electrophoretic analysis of DNA in Escherichia coli and leukocytes in plasma demonstrated enhanced DNA degradation in the presence of RB. UV light in combination with RB prevented the reactivation of lambda phage compared with samples irradiated in the absence of RB. UV-mediated oxidative damage in calf thymus DNA was also enhanced in the presence of RB. These observations clearly demonstrate that the presence of RB and UV light selectively enhances damage to the guanine bases in DNA. These data also suggest that the type and extent of damage to DNA for virus in the presence of RB and light make it less likely to be repaired by normal repair pathways available in host cells.
Published: 2004
Full Text: View/download PDF

42. Oxidative damage to DNA: formation, measurement and biochemical features

Author: Didier Gasparutto, Thierry Douki, Jean Cadet, Jean-Luc Ravanat, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Guanine, DNA damage, DNA repair, Health, Toxicology and Mutagenesis, Radical, Free radical damage to DNA, 010402 general chemistry, Radiation Dosage, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, DNA Adducts, Genetics, Animals, Humans, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Oligonucleotide, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Hydroxyl Radical, Combinatorial chemistry, 0104 chemical sciences, Oxygen, Oxidative Stress, Biochemistry, Radical ion, Mutagenesis, Reactive Oxygen Species, Oxidation-Reduction, DNA, DNA Damage
Abstract: Emphasis is placed in the first part of this survey on mechanistic aspects of the formation of 8-oxo-7,8-dihydroguanine (8-oxoGua) as the result of exposure to z.rad;OH radical, one-electron oxidants and singlet oxygen (1O(2)) oxidation. It was found that 8-oxoGua, which is generated by either hydration of the guanine radical cation or .OH addition at C8 of the imidazole ring, is a preferential target for further reactions with 1O(2) and one-electron oxidants, including the highly oxidizing oxyl-type guanine radical. Interestingly, tandem base lesions that involve 8-oxoGua and a vicinal formylamine residue were found to be generated within DNA as the result of a single .OH radical hit. The likely mechanism of formation of the latter lesions involves the transient generation of 5-(6)-peroxy-6-(5)-hydroxy-5,6-dihydropyrimidyl radicals that may add to the C8 of a vicinal guanine base before undergoing rearrangement. Another major topic which is addressed deals with recent developments in the measurement of oxidative base damage to cellular DNA. This was mostly achieved using the accurate and highly specific HPLC method coupled with the tandem mass spectrometry detection technique. Interestingly, optimized conditions of DNA extraction and subsequent work-up allow the accurate measurement of 11 modified nucleosides and bases within cellular DNA upon exposure to oxidizing agents including UVA and ionizing radiations. Finally, recently available data on the substrate specificity of DNA repair enzymes belonging to the base excision and nucleotide excision pathways are briefly reviewed. For this purpose modified oligonucleotides in which cyclopurine, and cyclopyrimidine nucleosides were site-specifically inserted were synthesized.
Published: 2003
Full Text: View/download PDF

43. Cross-Linked Thymine-Purine Base Tandem Lesions: Synthesis, Characterization, and Measurement in γ-Irradiated Isolated DNA

Author: Sophie Bellon, Didier Gasparutto, Jean Cadet, Jean-Luc Ravanat, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)
Subjects: Stereochemistry, Guanine, 010402 general chemistry, Toxicology, 01 natural sciences, Mass Spectrometry, Adduct, DNA Adducts, chemistry.chemical_compound, Animals, Moiety, Chromatography, High Pressure Liquid, ComputingMilieux_MISCELLANEOUS, Phosphoramidite, 010405 organic chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Methyl radical, Dose-Response Relationship, Radiation, DNA, General Medicine, 0104 chemical sciences, Thymine, Cross-Linking Reagents, chemistry, Gamma Rays, Purines, Cattle, Nucleoside, DNA Damage
Abstract: 5-(Phenylthiomethyl)-2'-deoxyuridine has been recently shown to be a specific photolabile precursor of 5-(2'-deoxyuridilyl)methyl radical that is involved in the formation of tandem base lesion with vicinal guanine in oxygen-free aqueous solution. The thionucleoside was incorporated by either liquid or solid-phase phosphoramidite synthesis into dinucleoside monophosphates with a 2'-deoxyadenosine residue as the vicinal nucleoside located either at the 3' or 5'-extremity. UV-C irradiation of the modified dinucleoside monophosphate under anaerobic conditions gives rise to cross-linked thymine(CH2-C8)adenine tandem base lesions which were isolated and characterized by (1)H NMR and mass spectrometry analyses. The formation of the latter tandem lesions involved an intramolecular addition of the 5-(2'-deoxyuridilyl)methyl radical to the C8 of the adenine moiety. A sensitive and specific assay aimed at monitoring the formation of the four thymine(CH2-C8)purine adducts, namely d(T Delta G), d(G Delta T), d(T Delta A), d(A Delta T), within DNA, was designed. This was based on a liquid chromatography analysis coupled to tandem mass spectrometry (HPLC-MS/MS) detection of the dinucleoside monophosphates which were quantitatively released from gamma-irradiated DNA and oligodeoxyribonucleotides by enzymatic hydrolysis. The four lesions were detected in both single-stranded oligodeoxyribonucleotide and isolated DNA upon exposure to gamma-radiation in oxygen-free aqueous solution. It was found that the tandem guanine-thymine lesions were produced more efficiently than the adenine-thymine cross-links. Moreover, a significant sequence effect was observed. Thus, the yield of formation of the tandem lesions is higher when the purine base is located at the 5' position of the 5-(2'-deoxyuridilyl)methyl radical.
Published: 2002
Full Text: View/download PDF

44. Inter-laboratory validation of procedures for measuring 8-oxo-7,8-dihydroguanine/8-oxo-7,8-dihydro-2’-deoxyguanosine in DNA

Author: C. Casalini, Nicole Phoa, Ruan M. Elliott, Jean-Luc Ravanat, Hiroshi Kasai, Rozenn Legall, Bénédicte Morin, Piero Dolara, Bente Jensen, Ana Lloret, Matthew J. Gordon, Christopher P. Wild, Bernd Epe, Rie Kido, Samantha Johnson, Karl E. Herbert, Eric Gremaud, Laura J. Hardie, Andrew Collins, Zdena Durackova, Rex M. Tyrrell, Siân Astley, Ryszard Olinski, Parul R. Patel, Henrik E. Poulsen, Laurent B. Fay, Pierre Duez, Andrea White, Pierre Cillard, Cristina Luceri, Annie Aarup Jensen, Csilla Mislanova, Michèle Tripier, Jean Cadet, Tim Hofer, Lucia Hlincíková, Mark D. Evans, Isabelle Morel, Henry Faure, Dina Chauhan, Angela Bailley, Chrisi Dunster, Ian D. Podmore, Karol Bialkowski, Odile Sergent, Jean-François Rees, Jose Viña, Francois Pognan, Peter Korytar, Allan Weimann, Anke Pelzer, Joseph Lunec, F. Guglielmi, Jacques Dubois, Thierry Douki, Frank J. Kelly, Catherine M. Gedik, Lennart Möller, Elizabeth C. Smith, Steffen Loft, Richard H. Stadler, Maria Dusinska, John O'Brien, Sharon G. Wood, Liliane Degand, Ann White, Julie Eakins, and Andrea Hartwig
Subjects: Guanine, Analytical chemistry, Test sensitivity, Thymus Gland, Sensitivity and Specificity, Biochemistry, Gas Chromatography-Mass Spectrometry, Mass Spectrometry, Oxidative dna damage, chemistry.chemical_compound, 8 oxo 7 8 dihydroguanine, Animals, Humans, European commission, Inter-laboratory, Chromatography, High Pressure Liquid, Chromatography, Chemistry, 8 oxo 7 8 dihydro 2 deoxyguanosine, DNA, General Medicine, Cattle, Biomarkers, Chromatography, Liquid, DNA Damage
Abstract: The aim of ESCODD, a European Commission funded Concerted Action, is to improve the precision and accuracy of methods for measuring 8-oxo-7,8-dihydroguanine (8-oxoGua) or the nucleoside (8-oxodG). On two occasions, participating laboratories received samples of different concentrations of 8-oxodG for analysis. About half the results returned (for 8-oxodG) were within 20% of the median values. Coefficients of variation (for three identical samples) were commonly around 10%. A sample of calf thymus DNA was sent, dry, to all laboratories. Analysis of 8-oxoGua/8-oxodG in this sample was a test of hydrolysis methods. Almost half the reported results were within 20% of the median value, and half obtained a CVof less than 10%. In order to test sensitivity, as well as precision, DNA was treated with photosensitiser and light to introduce increasing amounts of 8-oxoGua and samples were sent to members. Median values calculated from all returned results were 45.6 (untreated), 53.9, 60.4 and 65.6 8-oxoGua/10(6) Gua; only seven laboratories detected the increase over the whole range, while all but one detected a dose response over two concentration intervals. Results in this trial reflect a continuing improvement in precision and accuracy. The next challenge will be the analysis of 8-oxodG in DNA isolated from cells or tissue, where the concentration is much lower than in calf thymus DNA.
Published: 2002
Full Text: View/download PDF

45. Cellular background level of 8-oxo-7,8-dihydro-2 '-deoxyguanosine: an isotope based method to evaluate artefactual oxidation of DNA during its extraction and subsequent work-up

Author: Jean-Luc Ravanat, Lydie Lasserre, Karl E. Herbert, Thierry Douki, Eric Gremaud, Alain Favier, Pierre Duez, Jean Cadet, Tim Hofer, Christine Saint-Pierre, Douki, Thierry, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Cancer Research, Lysis, Oxygen Isotopes, Antioxidants, Mass Spectrometry, Monocytes, Nucleobase, chemistry.chemical_compound, 0302 clinical medicine, Reference Values, Tumor Cells, Cultured, Chemical Precipitation, Deoxyguanosine, Chromatography, High Pressure Liquid, Chelating Agents, 0303 health sciences, Singlet Oxygen, DNA, Neoplasm, General Medicine, Reference Standards, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Liver, Biochemistry, 8-Hydroxy-2'-Deoxyguanosine, 030220 oncology & carcinogenesis, Sodium iodide, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Leukemia, Monocytic, Acute, Artifacts, Oxidation-Reduction, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, Sodium Iodide, Thymus Gland, Deferoxamine, Cell Fractionation, Cyclic N-Oxides, 03 medical and health sciences, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Animals, 030304 developmental biology, Chromatography, DNA, DNA oxidation, DNA extraction, Rats, chemistry, Cattle, Nucleoside, DNA Damage
Abstract: The measurement of oxidative damage to cellular DNA is a challenging analytical problem requiring highly sensitive and specific methods. In addition, artefactual DNA oxidation during its extraction and subsequent work-up may give rise to overestimated levels of oxidized DNA bases. In the present study, we have used (18)O-labelled 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) as an internal standard to evaluate the extent of artefactual DNA oxidation during the critical steps preceding the measurement. The labelled oxidized purine nucleoside was specifically generated in cellular DNA using the recently available generator of (18)O-labelled singlet oxygen. Artefactual DNA oxidation that could take place during the work-up increases the level of 8-oxodGuo but not of the (18)O-oxidized nucleoside. Therefore, the ratio between the two compounds, as measured by high performance liquid chromatography coupled to tandem mass spectrometry, allows an unambiguous comparison of different methodologies. The comparison of different DNA extraction protocols led to the conclusion that artefactual DNA oxidation during the extraction step could be minimized if: (i) nuclei are isolated after cell lysis; (ii) desferrioxamine, a transition metal chelator is added to the different extraction buffers; and (iii) sodium iodide (or alternatively guanidine thiocyanate) is used for DNA precipitation. It was also demonstrated that sodium iodide does not decompose the targeted oxidized purine nucleoside. In addition, three different DNA digestion protocols were evaluated and they were found to give rise to similar results. Using the best-studied protocol, the steady-state cellular background level of 8-oxodGuo, in a lymphocyte cell line, was determined to be approximately 0.5 lesions/10(6) DNA nucleosides.
Published: 2002

46. Direct and indirect effects of UV radiation on DNA and its components

Author: Thierry Douki, Jean Cadet, Jean-Luc Ravanat, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Douki, Thierry
Subjects: [CHIM.ANAL] Chemical Sciences/Analytical chemistry, Pyrimidine, Ultraviolet Rays, Guanine, DNA damage, Biophysics, Free radical damage to DNA, Endogeny, 010402 general chemistry, Photochemistry, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Animals, Humans, Radiology, Nuclear Medicine and imaging, 030304 developmental biology, 0303 health sciences, Radiation, Radiological and Ultrasound Technology, Singlet oxygen, DNA, 0104 chemical sciences, [SDV.TOX] Life Sciences [q-bio]/Toxicology, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Nucleic acid, sense organs, Oxidation-Reduction
Abstract: In this survey, emphasis was placed on the main photoreactions of nucleic acid components, involving both direct and indirect effects. The main UVB- and UVA-induced DNA photoproducts, together with the mechanisms of their formation, are described. Information on the photoproduct distribution within cellular DNA is also provided, taking into account the limitations of the different analytical methods applied to monitor the formation of the DNA damage. Thus, the formation of the main DNA dimeric pyrimidine lesions produced by direct absorption of UVB photons was assessed using a powerful HPLC-tandem mass spectrometry assay. In addition, it was found that UVA photooxidation damage mostly involves the guanine residues of cellular DNA as the result of singlet oxygen generation by still unknown endogenous photosensitizers.
Published: 2001

47. 2′-deoxyguanosine oxidation is associated with decrease in the DNA-binding activity of the transcription factor Sp1 in liver and kidney from diabetic and insulin-resistant rats

Author: Jean-Luc Ravanat, Patrice Faure, Marie Joyeux, Olivier Ramon, Alain Favier, Jean Cadet, Serge Halimi, Jacqueline Riondel, Heng-Kuan Wong, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Male, medicine.medical_specialty, Sp1 Transcription Factor, DNA damage, Fructose, Kidney, medicine.disease_cause, Biochemistry, Diabetes Mellitus, Experimental, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Animals, Deoxyguanosine, Rats, Wistar, Transcription factor, Chromatography, High Pressure Liquid, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, [CHIM.ORGA]Chemical Sciences/Organic chemistry, NF-kappa B, 8-Hydroxy-2'-deoxyguanosine, DNA, Glutathione, DNA oxidation, Diet, Rats, Endocrinology, Liver, chemistry, 8-Hydroxy-2'-Deoxyguanosine, 030220 oncology & carcinogenesis, Insulin Resistance, Reactive Oxygen Species, Oxidation-Reduction, Oxidative stress
Abstract: Over the years, several lines of evidence have emerged supporting the role of oxidative stress in the development of diabetic complications. This could involve the increase in the production of reactive oxygen species and the decrease in antioxidative defense systems. Modulation of the level of intracellular reactive oxygen species is likely to affect the intracellular redox homeostasis, which is crucial for numerous biological events such as the transcriptional activation of genes. In this work we studied the binding of the redox transcription factors Sp1 and NF-kappaB extracted from kidney and liver of streptozotocin diabetic (STZ) and fructose-fed rats using electrophoretic mobility shift (EMSA) assay. In addition, the level in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) was assessed within DNA by high performance liquid chromatography with electrochemical detection (HPLC-EC). A decrease in the affinity of Sp1 to DNA was observed in the kidney of STZ rats and fructose-fed rats (15% +/- 8.3 and 54% +/- 6.9, respectively, versus control group set to 100%). This was also found to occur to a lower extent, in the liver. Interestingly, higher levels of 8-oxodGuo, a biomarker of DNA oxidation, were measured in the kidney of diabetic rats. Therefore, the modification in the binding efficiency of Sp1 or NF-kappaB could be related to reactive oxygen species-mediated DNA damage.
Published: 2001
Full Text: View/download PDF

48. Facts and artifacts in the measurement of oxidative base damage to DNA

Author: Sylvie Sauvaigo, Jean-Luc Ravanat, Thierry Douki, Cédric d'Ham, Jean-Pierre Pouget, Jean Cadet, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: DNA Repair, Oxidative phosphorylation, Mass spectrometry, High-performance liquid chromatography, Biochemistry, Gas Chromatography-Mass Spectrometry, Oxidative dna damage, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cellular dna, Animals, Humans, Derivatization, Base Pairing, ComputingMilieux_MISCELLANEOUS, Chromatography, High Pressure Liquid, 030304 developmental biology, 0303 health sciences, Chromatography, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Deoxyguanosine, General Medicine, Endonucleases, Oxidative Stress, 8-Hydroxy-2'-Deoxyguanosine, 030220 oncology & carcinogenesis, Isotope Labeling, Gas chromatography, Oxidation-Reduction, Phosphorus Radioisotopes, DNA, DNA Damage
Abstract: This short survey is aimed at critically evaluating the main available methods for measuring oxidative base damage within cellular DNA. Emphasis is placed on separative methods which are currently widely applied. These mostly concern high performance liquid chromatography (HPLC) and gas chromatography (GC) associated with sensitive detection techniques such as electrochemistry (EC) and mass spectrometry (MS). In addition, the comparison is extended to 32p-postlabeling methods, immunoassays and measurement of two main classes of oxidative DNA damage within isolated cells. It may be concluded that the HPLC-electrochemical detection (ECD) method, even if restricted to the measurement of only a few electroactive oxidized bases and nucleosides, is the simplest and safest available method at the moment. In contrast, the more versatile GC-MS method, which requires a HPLC pre-purification step in order to prevent artifactual oxidation of overwhelming normal bases to occur during derivatization, is more tedious and its sensitivity may be questionable. Alternative simpler procedures of background prevention for the GC-MS assay, which, however, remain to be validated, include low-temperature for derivatization and addition of antioxidants to the silylating reagents. Interestingly, similar levels of 8-oxo-7,8-dihydroguanine were found in cellular DNA using HPLC-ECD, HPLC-MS/MS and HPLC/32P-postlabeling methods. However, it should be noted that the level of cellular 8-oxodGuo, thus determined, is on average basis 10-fold higher than that was inferred for more indirect measurement involving the use of DNA repair enzymes with methods on isolated cells. Further efforts should be made to resolve this apparent discrepancy. In addition, the question of the biological validation of the non-invasive measurement of oxidized bases and nucleosides in urine is addressed.
Published: 1999
Full Text: View/download PDF

49. Hydroxyl radicals and DNA base damage

Author: Jean Cadet, Jean-Pierre Pouget, Jean-Luc Ravanat, Sylvie Sauvaigo, Thierry Delatour, Thierry Douki, Didier Gasparutto, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Pyrimidine, DNA damage, Guanine, Health, Toxicology and Mutagenesis, 010402 general chemistry, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Genetics, Animals, Humans, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Oligonucleotide, Hydroxyl Radical, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Mutagenesis, 0104 chemical sciences, Thymine, Oxidative Stress, chemistry, Biochemistry, Reactive Oxygen Species, Oxidation-Reduction, DNA, Cytosine, DNA Damage
Abstract: Modified purine and pyrimidine bases constitute one of the major classes of hydroxyl-radical-mediated DNA damage together with oligonucleotide strand breaks, DNA-protein cross-links and abasic sites. A comprehensive survey of the main available data on both structural and mechanistic aspects of.OH-induced decomposition pathways of both purine and pyrimidine bases of isolated DNA and model compounds is presented. In this respect, detailed information is provided on both thymine and guanine whereas data are not as complete for adenine and cytosine. The second part of the overview is dedicated to the formation of.OH-induced base lesions within cellular DNA and in vivo situations. Before addressing this major point, the main available methods aimed at singling out.OH-mediated base modifications are critically reviewed. Unfortunately, it is clear that the bulk of the chemical and biochemical assays with the exception of the high performance liquid chromatographic-electrochemical detection (HPLC/ECD) method have suffered from major drawbacks. This explains why there are only a few available accurate data concerning both the qualitative and quantitative aspects of the.OH-induced formation of base damage within cellular DNA. Therefore, major efforts should be devoted to the reassessment of the level of oxidative base damage in cellular DNA using appropriate assays including suitable conditions of DNA extraction.
Published: 1999
Full Text: View/download PDF

50. Effects of UV and visible radiation on DNA-final base damage

Author: Cadet J, Berger M, Douki T, Morin B, Raoul S, Jean-Luc RAVANAT, and Spinelli S
Subjects: Base Composition, Guanine, Light, Molecular Structure, Ultraviolet Rays, Sunlight, Animals, Humans, DNA, Oxidation-Reduction, DNA Damage, Forecasting
Abstract: Several mechanisms are likely to be involved in the solar radiation-mediated modifications of cellular DNA. Direct excitation of DNA bases by the UVB component (290-320 nm) of solar light gives rise, mostly through oxygen independent reactions, to the formation of dimeric pyrimidine lesions including cyclobutadipyrimidines, pyrimidine (6-4) pyrimidone photoproducts and related valence Dewar isomers. In addition, photoexcitation of cytosine and guanine may lead to the formation in relatively minor yields of 6-hydroxy-5,6-dihydrocytosine and 8-oxo-7,8-dihydroguanine, respectively. A second mechanism that requires the participation of endogenous photosensitizers together with oxygen is at the origin of most of the DNA damage generated by the UVA (320-400 nm) and visible light. Singlet oxygen, which arises from a type II mechanism, is likely to be mostly involved in the formation of 8-oxo-7,8-dihydroguanine that was observed within both isolated and cellular DNA. However, it may be expected that the latter oxidized purine lesion together with DNA strand breaks and pyrimidine base oxidation products are also generated with a lower efficiency through Fenton type reactions. A more definitive assessment of these mechanisms would require further studies aimed at the identification and quantification of the different DNA photolesions including both dimeric pyrimidine photoproducts and photooxidized lesions.
Published: 1998

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

55 results on '"Jean-Luc Ravanat"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources