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1. The thiolation of uridine 34 in tRNA, which controls protein translation, depends on a [4Fe-4S] cluster in the archaeum Methanococcus maripaludis

Author

Ornella Bimai, Pierre Legrand, Jean-Luc Ravanat, Nadia Touati, Jingjing Zhou, Nisha He, Marine Lénon, Frédéric Barras, Marc Fontecave, and Béatrice Golinelli-Pimpaneau

Subjects
Medicine, Science
Abstract

Abstract Thiolation of uridine 34 in the anticodon loop of several tRNAs is conserved in the three domains of life and guarantees fidelity of protein translation. U34-tRNA thiolation is catalyzed by a complex of two proteins in the eukaryotic cytosol (named Ctu1/Ctu2 in humans), but by a single NcsA enzyme in archaea. We report here spectroscopic and biochemical experiments showing that NcsA from Methanococcus maripaludis (MmNcsA) is a dimer that binds a [4Fe-4S] cluster, which is required for catalysis. Moreover, the crystal structure of MmNcsA at 2.8 Å resolution shows that the [4Fe-4S] cluster is coordinated by three conserved cysteines only, in each monomer. Extra electron density on the fourth nonprotein-bonded iron most likely locates the binding site for a hydrogenosulfide ligand, in agreement with the [4Fe-4S] cluster being used to bind and activate the sulfur atom of the sulfur donor. Comparison of the crystal structure of MmNcsA with the AlphaFold model of the human Ctu1/Ctu2 complex shows a very close superposition of the catalytic site residues, including the cysteines that coordinate the [4Fe-4S] cluster in MmNcsA. We thus propose that the same mechanism for U34-tRNA thiolation, mediated by a [4Fe-4S]-dependent enzyme, operates in archaea and eukaryotes.

Published
2023
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2. Enhancement of IUdR Radiosensitization by Low-Energy Photons Results from Increased and Persistent DNA Damage.

Author

Emilie Bayart, Frédéric Pouzoulet, Lucie Calmels, Jonathan Dadoun, Fabien Allot, Johann Plagnard, Jean-Luc Ravanat, André Bridier, Marc Denozière, Jean Bourhis, and Eric Deutsch

Subjects
Medicine, Science
Abstract

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 137Cs 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 halogenated pyrimidine analog combined with low-energy X-ray therapy.

Published
2017
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3. Low doses of gamma-irradiation induce an early bystander effect in zebrafish cells which is sufficient to radioprotect cells.

Author

Sandrine Pereira, Véronique Malard, Jean-Luc Ravanat, Anne-Hélène Davin, Jean Armengaud, Nicolas Foray, and Christelle Adam-Guillermin

Subjects
Medicine, Science
Abstract

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 γ-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 γ-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 γ-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
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4. Iron–sulfur biology invades tRNA modification: the case of U34 sulfuration

Author

Karolina Podskoczyj, Christophe Velours, Grazyna Leszczynska, Jingjing Zhou, Marine Lénon, Marc Fontecave, Jean-Luc Ravanat, Béatrice Golinelli-Pimpaneau, Nadia Touati, Frédéric Barras, 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), Laboratoire de Chimie des Processus Biologiques (LCPB), Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Adaptation au stress et Métabolisme chez les entérobactéries - Stress adaptation and metabolism in enterobacteria (SAMe), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Institut de Recherche de Chimie Paris (IRCP), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ministère de la Culture (MC), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), University of Lódź, ANR-11-LABX-0011,DYNAMO,Dynamique des membranes transductrices d'énergie : biogénèse et organisation supramoléculaire.(2011), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC)

Subjects
chemistry.chemical_classification, 0303 health sciences, TRNA modification, AcademicSubjects/SCI00010, Nucleic Acid Enzymes, [CHIM.ORGA]Chemical Sciences/Organic chemistry, [SDV]Life Sciences [q-bio], 030302 biochemistry & molecular biology, Mutagenesis, Biology, medicine.disease_cause, Uridine, 03 medical and health sciences, chemistry.chemical_compound, Enzyme, Biosynthesis, chemistry, Biochemistry, Transfer RNA, Genetics, medicine, Escherichia coli, Nucleoside, 030304 developmental biology
Abstract

Sulfuration of uridine 34 in the anticodon of tRNAs is conserved in the three domains of life, guaranteeing fidelity of protein translation. In eubacteria, it is catalyzed by MnmA-type enzymes, which were previously concluded not to depend on an iron–sulfur [Fe–S] cluster. However, we report here spectroscopic and iron/sulfur analysis, as well as in vitro catalytic assays and site-directed mutagenesis studies unambiguously showing that MnmA from Escherichia coli can bind a [4Fe–4S] cluster, which is essential for sulfuration of U34-tRNA. We propose that the cluster serves to bind and activate hydrosulfide for nucleophilic attack on the adenylated nucleoside. Intriguingly, we found that E. coli cells retain s2U34 biosynthesis in the ΔiscUA ΔsufABCDSE strain, lacking functional ISC and SUF [Fe–S] cluster assembly machineries, thus suggesting an original and yet undescribed way of maturation of MnmA. Moreover, we report genetic analysis showing the importance of MnmA for sustaining oxidative stress.

Published
2021
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5. Radiation Dose-Enhancement Is a Potent Radiotherapeutic Effect of Rare-Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma

Author

Dennis Brueckner, Sylvain Bohic, Benoit Busser, Lucie Sancey, Frédéric Chaput, Vincent Motto-Ros, Frédéric Lerouge, Jan Garrevoet, Jean-Luc Ravanat, Mans Broekgaarden, Hélène Elleaume, Christophe Dujardin, Victor Baisamy, Antonia Youssef, Anne-Laure Bulin, Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Chimie - UMR5182 (LC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC), Deutsches Elektronen-Synchrotron [Zeuthen] (DESY), Helmholtz-Gemeinschaft = Helmholtz Association, Cancer Targets & Experimental Therapeutics, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-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)-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), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Luminescence (LUMINESCENCE), Institut Lumière Matière [Villeurbanne] (ILM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Spectrométrie des biomolécules et agrégats (SPECTROBIO), ANR-11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011), ANR-11-INBS-0006,FLI,France Life Imaging(2011), Lerouge, Frédéric, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), European Synchroton Radiation Facility [Grenoble] (ESRF), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Rayet, Béatrice, Physique, Radiobiologie, Imagerie Médicale et Simulation - - PRIMES2011 - ANR-11-LABX-0063 - LABX - VALID, Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID, and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
Materials science, General Chemical Engineering, medicine.medical_treatment, Rare earth, GLIOBLASTOMA, General Physics and Astronomy, Medicine (miscellaneous), Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Biochemistry, Genetics and Molecular Biology (miscellaneous), radiation dose‐enhancement, RADIATION THERAPY, [SDV.CAN] Life Sciences [q-bio]/Cancer, Radioresistance, medicine, General Materials Science, lcsh:Science, Full Paper, synchrotron radiation, Spatially resolved, Radiation dose, X‐ray‐induced photodynamic therapy, General Engineering, glioblastoma, Full Papers, RADIATION DOSE ENHANCEMENT, 021001 nanoscience & nanotechnology, medicine.disease, 0104 chemical sciences, 3. Good health, NANOSCINTILLATORS, Radiation therapy, nanoscintillators, Photoelectric absorption, Cancer research, lcsh:Q, 0210 nano-technology, Glioblastoma, ddc:624
Abstract

Advanced science xx, 2001675 (1-18) (2020). doi:10.1002/advs.202001675, To improve the prognosis of glioblastoma, innovative radiotherapy regimens are required to augment the effect of tolerable radiation doses while sparing surrounding tissues. In this context, nanoscintillators are emerging radiotherapeutics that down‐convert X‐rays into photons with energies ranging from UV to near‐infrared. During radiotherapy, these scintillating properties amplify radiation‐induced damage by UV‐C emission or photodynamic effects. Additionally, nanoscintillators that contain high‐Z elements are likely to induce another, currently unexplored effect: radiation dose‐enhancement. This phenomenon stems from a higher photoelectric absorption of orthovoltage X‐rays by high‐Z elements compared to tissues, resulting in increased production of tissue‐damaging photo‐ and Auger electrons. In this study, Geant4 simulations reveal that rare‐earth composite LaF$_3$:Ce nanoscintillators effectively generate photo‐ and Auger‐electrons upon orthovoltage X‐rays. 3D spatially resolved X‐ray fluorescence microtomography shows that LaF$_3$:Ce highly concentrates in microtumors and enhances radiotherapy in an X‐ray energy‐dependent manner. In an aggressive syngeneic model of orthotopic glioblastoma, intracerebral injection of LaF$_3$:Ce is well tolerated and achieves complete tumor remission in 15% of the subjects receiving monochromatic synchrotron radiotherapy. This study provides unequivocal evidence for radiation dose‐enhancement by nanoscintillators, eliciting a prominent radiotherapeutic effect. Altogether, nanoscintillators have invaluable properties for enhancing the focal damage of radiotherapy in glioblastoma and other radioresistant cancers., Published by Wiley-VCH, Weinheim

Published
2020
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6. Impairment of Base Excision Repair in Dermal Fibroblasts Isolated From Nevoid Basal Cell Carcinoma Patients

Author

Aurélie Charazac, Nour Fayyad, David Beal, Sandrine Bourgoin-Voillard, Michel Seve, Sylvie Sauvaigo, Jérôme Lamartine, Pascal Soularue, Sandra Moratille, Michèle T. Martin, Jean-Luc Ravanat, Thierry Douki, Walid Rachidi, 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), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), LXRepair, Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Génomique et Radiobiologie de la Kératinopoïèse, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Douki, Thierry

Subjects
0301 basic medicine, Cancer Research, Tumor suppressor gene, DNA repair, DNA damage, Nevoid basal-cell carcinoma syndrome, lcsh:RC254-282, base excision repair, PTCH1 mutation, 03 medical and health sciences, 0302 clinical medicine, nevoid basal cell carcinoma syndrome, medicine, Basal cell carcinoma, Radiosensitivity, ROS production, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Original Research, business.industry, Base excision repair, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, stomatognathic diseases, 030104 developmental biology, PTCH1, Oncology, 030220 oncology & carcinogenesis, Cancer research, business
Abstract

International audience; The nevoid basal cell carcinoma syndrome (NBCCS), also called Gorlin syndrome is an autosomal dominant disorder whose incidence is estimated at about 1 per 55,600–256,000 individuals. It is characterized by several developmental abnormalities and an increased predisposition to the development of basal cell carcinomas (BCCs). Cutaneous fibroblasts from Gorlin patients have been shown to exhibit an increased sensitivity to ionizing radiations. Mutations in the tumor suppressor gene PTCH1, which is part of the Sonic Hedgehog (SHH) signaling pathway, are responsible for these clinical manifestations. As several genetic mutations in the DNA repair genes are responsible of photo or radiosensitivity and high predisposition to cancers, we hypothesized that these effects in Gorlin syndrome might be due to a defect in the DNA damage response (DDR) and/or the DNA repair capacities. Therefore, the objective of this work was to investigate the sensitivity of skin fibroblasts from NBCCS patients to different DNA damaging agents and to determine the ability of these agents to modulate the DNA repair capacities. Gorlin fibroblasts showed high radiosensitivity and also less resistance to oxidative stress-inducing agents when compared to control fibroblasts obtained from healthy individuals. Gorlin fibroblasts harboring PTCH1 mutations were more sensitive to the exposure to ionizing radiation and to UVA. However, no difference in cell viability was shown after exposure to UVB or bleomycin. As BER is responsible for the repair of oxidative DNA damage, we decided to assess the BER pathway efficacy in Gorlin fibroblasts. Interestingly, a concomitant decrease of both BER gene expression and BER protein activity was observed in Gorlin fibroblasts when compared to control. Our results suggest that low levels of DNA repair within Gorlin cells may lead to an accumulation of oxidative DNA damage that could participate and partly explain the radiosensitivity and the BCC-prone phenotype in Gorlin syndrome.

Published
2020
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7. Endogenous natural and radiation-induced DNA lesions: differences and similarities and possible implications for human health and radiological protection

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
0301 basic medicine, DNA repair, DNA damage, Health, Toxicology and Mutagenesis, Endogeny, Biology, medicine.disease_cause, Bioinformatics, Ionizing radiation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Safety, Risk, Reliability and Quality, Waste Management and Disposal, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Renewable Energy, Sustainability and the Environment, Public Health, Environmental and Occupational Health, Review article, genomic DNA, 030104 developmental biology, Nuclear Energy and Engineering, chemistry, 030220 oncology & carcinogenesis, DNA, Oxidative stress
Abstract

International audience; During the last few decades, a considerable amount of work has been done to better assess the effects of ionizing radiation on living organisms. In particular a lot of attention has been focused on the consequences of modifications of the DNA macromolecule, the support of the genetic information. Detailed information is now available on the formation of radiation-induced DNA lesions at the physical, chemical and biological levels. Emphasis will be placed in this review article on the differences and similarities, in term of DNA lesions formation and outcome, between endogenous oxidative stress and ionizing radiation, both stresses that could produce oxidative DNA lesions through similar mechanistic pathways involving mostly reactive oxygen species. If the chemical nature of the generated lesions is similar, the differences in term of biological consequences could be attributed to their spatial distribution in genomic DNA, since ionizing radiations produce lesions in cluster. These clusters of lesions represent a challenge for the DNA repair machinery. In contrast, endogenous oxidative stress generates scattered lesions that could be repaired with a much higher efficacy and fidelity. Possible implication of the use of DNA damage and repair for human health purposes and radiological protection will be discussed.

Published
2018
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8. Radioluminescent nanomaterials to induce deep-tissue PDT: towards a complete description of the therapeutic contributions (Conference Presentation)

Author

Tayyaba Hasan, Lucie Sancey, Frédéric Chaput, Mans Broekgaarden, Jean-Luc Ravanat, H. Elleaume, and Anne-Laure Bulin

Subjects
030207 dermatology & venereal diseases, 0303 health sciences, 03 medical and health sciences, Presentation, 0302 clinical medicine, Deep tissue, business.industry, media_common.quotation_subject, 030303 biophysics, Medicine, Nanotechnology, business, media_common
Published
2019
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9. 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
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10. 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
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11. 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
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12. Ionizing radiation biomarkers in epidemiological studies – An update

Author

Jean-Luc Ravanat, Mohammed Abderrafi Benotmane, Julia Hess, Eileen Pernot, Dominique Laurier, Bjorn Baselet, Olivier Laurent, Sarah Baatout, Mats Harms-Ringhdahl, Penny A. Jeggo, Grainne Manning, Maria Gomolka, Roel Quintens, Tamara V. Azizova, Horst Zitzelsberger, Catharine M L West, An Aerts, Yann Gueguen, Christophe Badie, Soile Tapio, Laure Sabatier, Eric Blanchardon, Natasa Anastasov, Omid Azimzadeh, Ellina Macaeva, Michaela Kreuzer, Janet Hall, Karine Tack, Elisabeth Cardis, Siamak Haghdoost, 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), Centre for Genome Damage and Stability, University of Sussex, Translational Radiobiology Group, The University of Manchester, Department of Transitional Medicine, Oxford Road, Manchester, M13 9PL, Federal Office for Radiation Protection (BfS), Radiobiology Unit, Belgian Nuclear Research Centre, Public Health England [London], Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Helmholtz-Zentrum München (HZM), Southern Urals Biophysics Institute, Department of Biomedical Molecular Biology [Ghent], Universiteit Gent = Ghent University [Belgium] (UGENT), Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain = Catholic University of Louvain (UCL)-Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University-The Wenner-Gren Institute, Stockholm University, Epidemiologie-Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], 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'Energie Atomique (CEA), DRF/PROCyTOX , Fontenay-aux-Roses , France., ommissariat à l'Energie Atomique (CEA), DRF/PROCyTOX , Fontenay-aux-Roses , France. Code (UMR, EA, ...), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, European Project: 249689,EC:FP7:Fission,FP7-Fission-2009,DOREMI(2010), Bundesamt für Strahlenschutz - Federal Office for Radiation Protection (BfS), Helmholtz Zentrum München = German Research Center for Environmental Health, Universiteit Gent = Ghent University (UGENT), Stockholm University-Stockholm University, 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, Oncology, Adult, Ionizing radiation, medicine.medical_specialty, Effects, DNA Repair, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Biology, Radiation Dosage, Exposure, Toxicology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Radiation, Ionizing, Epidemiology, Genetics, medicine, Humans, Genetic Predisposition to Disease, Low dose rate, Stage (cooking), Child, Paediatric patients, Solid tumour, Individual sensitivity, Radiació ionitzant, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Potential biomarkers, Molecular epidemiology, Marcadors bioquímics, Biomarker (medicine), [CHIM.RADIO]Chemical Sciences/Radiochemistry, Biomarkers, Individual Sensitivity, Ionizing Radiation, Molecular Epidemiology, DNA Damage
Abstract

Recent epidemiology studies highlighted the detrimental health effects of exposure to low dose and low dose rate ionizing radiation (IR): nuclear industry workers studies have shown increased leukaemia and solid tumour risks following cumulative doses of

Published
2017
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13. Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors

Author

Olivier A. Bernard, François Delhommeau, Eric Solary, Frédéric Pendino, Nicole Casadevall, Lucy A. Godley, Bruno Carbonne, Elodie Pronier, Jérôme Larghero, Aparna Vasanthakumar, William Vainchenker, Barbara da Costa Reis Monte Mor, Carole Almire, Isabelle Plo, Jean-Luc Ravanat, Aline Massé, Jean-Pierre Le Couedic, Nathalie Droin, Hayat Mokrani, Audrey Simon, 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, Myeloid, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Immunology, CD34, Cell Biology, Hematology, Biology, medicine.disease, Biochemistry, 3. Good health, 03 medical and health sciences, Haematopoiesis, Leukemia, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cord blood, medicine, Cancer research, Myelopoiesis, Stem cell, Myeloproliferative neoplasm, 030304 developmental biology
Abstract

TET2 converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) in DNA and is frequently mutated in myeloid malignancies, including myeloproliferative neoplasms. Here we show that the level of 5-hmC is decreased in granulocyte DNA from myeloproliferative neoplasm patients with TET2 mutations compared with granulocyte DNA from healthy patients. Inhibition of TET2 by RNA interference decreases 5-hmC levels in both human leukemia cell lines and cord blood CD34+ cells. These results confirm the enzymatic function of TET2 in human hematopoietic cells. Knockdown of TET2 in cord blood CD34+ cells skews progenitor differentiation toward the granulomonocytic lineage at the expense of lymphoid and erythroid lineages. In addition, by monitoring in vitro granulomonocytic development we found a decreased granulocytic differentiation and an increase in monocytic cells. Our results indicate that TET2 disruption affects 5-hmC levels in human myeloid cells and participates in the pathogenesis of myeloid malignancies through the disturbance of myeloid differentiation.

Published
2011
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14. Oxidative Stress, DNA Damage, and Inflammation Induced by Ambient Air and Wood Smoke Particulate Matter in Human A549 and THP-1 Cell Lines

Author

Theo M. de Kok, Pernille Høgh Danielsen, Anoop Kumar Sharma, Herman Autrup, Jacob J. Briedé, Peter Møller, Jean-Luc Ravanat, Steffen Loft, Rossana Bossi, Lars Mølhave, Håkan Wallin, Keld Alstrup Jensen, 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), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Toxicogenomics, and RS: GROW - School for Oncology and Reproduction

Subjects
DNA damage, Gene Expression, 010501 environmental sciences, Toxicology, medicine.disease_cause, Combustion, 01 natural sciences, Cell Line, 03 medical and health sciences, Smoke, medicine, Humans, Particle Size, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0105 earth and related environmental sciences, Inflammation, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, Cell Death, [CHIM.ORGA]Chemical Sciences/Organic chemistry, General Medicine, Formamidopyrimidine DNA glycosylase, Particulates, Wood, Comet assay, Oxidative Stress, chemistry, 13. Climate action, Environmental chemistry, Toxicity, Reactive Oxygen Species, Oxidative stress, DNA Damage
Abstract

Combustion of biomass and wood for residential heating and/or cooking contributes substantially to both ambient air and indoor levels of particulate matter (PM). Toxicological characterization of ambient air PM, especially related to traffic, is well advanced, whereas the toxicology of wood smoke PM (WSPM) is poorly assessed. We assessed a wide spectrum of toxicity end points in human A549 lung epithelial and THP-1 monocytic cell lines comparing WSPM from high or low oxygen combustion and ambient PM collected in a village with many operating wood stoves and from a rural background area. In both cell types, all extensively characterized PM samples (1.25-100 mu g/mL) induced dose-dependent formation of reactive oxygen species and DNA damage in terms of strand breaks and formamidopyrimidine DNA glycosylase sites assessed by the comet assay with WSPM being most potent. The WSPM contained more polycyclic aromatic hydrocarbons (PAH), less soluble metals, and expectedly also had a smaller particle size than PM collected from ambient air. All four types of PM combined increased the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine dose-dependently in A549 cells, whereas there was no change in the levels of etheno-adducts or bulky DNA adducts. Furthermore, mRNA expression of the proinflammatory genes monocyte chemoattractant protein-1, interleukin-8, and tumor necrosis factor-alpha as well as the oxidative stress gene heme oxygenase-1 was upregulated in the THP-1 cells especially by WSPM and ambient PM sampled from the wood stove area. Expression of oxoguanine glycosylase 1, lymphocyte function-associated antigen-1, and interleukin-6 did not change. We conclude that WSPM has small particle size, high level of PAR, low level of water-soluble metals, and produces high levels of free radicals, DNA damage as well as inflammatory and oxidative stress response gene expression in cultured human cells.

Published
2011
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15. 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
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16. COST Action CM1201 'Biomimetic Radical Chemistry': free radical chemistry successfully meets many disciplines

Author

Jean-Luc Ravanat, Carla Ferreri, Ullrich Jahn, Bernard T. Golding, ISOF Bio Free Radicals, Consiglio Nazionale delle Ricerche [Bologna] (CNR), School of Chemistry [Newcastle], Newcastle University [Newcastle], Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB / CAS), Czech Academy of Sciences [Prague] (CAS), 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
0301 basic medicine, Research groups, Free Radicals, Radical, Nanotechnology, Biochemistry, phospholipid remodeling, 03 medical and health sciences, Biomimetics, membrane stress, Humans, Medicine, Cost action, bio-inspired synthetic methodologies, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Radical enzyme, business.industry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Membrane stress, DNA damage and repair, General Medicine, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, biomimetic models, Engineering ethics, Working group, business
Abstract

International audience; The COST Action CM1201 “Biomimetic Radical Chemistry” has been active since December 2012 for 4 years, developing research topics organized into four working groups: WG1 – Radical Enzymes, WG2 – Models of DNA damage and consequences, WG3 – Membrane stress, signalling and defenses, and WG4 – Bio-inspired synthetic strategies. International collaborations have been established among the participating 80 research groups with brilliant interdisciplinary achievements. Free radical research with a biomimetic approach has been realized in the COST Action and are summarized in this overview by the four WG leaders.

Published
2016
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17. 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
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18. 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
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19. 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
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20. 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
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21. Quantification of DNA Damage Using Mass Spectrometry Techniques

Author

Jean-Luc Ravanat, Thierry Douki, 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, Mutation, Chromatography, Modified dna, DNA damage, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Chemical structure, 010401 analytical chemistry, medicine.disease_cause, Mass spectrometry, 01 natural sciences, 0104 chemical sciences, 03 medical and health sciences, chemistry.chemical_compound, chemistry, Chemical agents, medicine, DNA, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

The role of DNA in cells relies on its chemical structure. Unfortunately, a number of physical and chemical agents may damage DNA, leading to modification of genetic information or to cell death. Detecting DNA damage is thus a major issue in numerous studies. Analytical methods have therefore been developed in order to quantify modified DNA bases. In particular, mass spectrometry is used as a very specific and sensitive detector when combined to gas or liquid chromatography. This review will first briefly present the major classes of DNA damage and then focus on two mass spectrometry-based approaches for the quantification of modified bases following DNA hydrolysis into monomers.

Published
2014
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22. DNA binding of the p21 repressor ZBTB2 is inhibited by cytosine hydroxymethylation

Author

Christine Saint-Pierre, Audrey Miscioscia, Jean-Luc Ravanat, Céline Lafaye, Jean Breton, Alexandra Kraut, Ewa Barbier, Didier Gasparutto, Yohann Couté, Isabelle Plo, 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 d'étude de la dynamique des protéomes (LEDyP), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ravanat, Jean-Luc, 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 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 National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Cyclin-Dependent Kinase Inhibitor p21, Biophysics, Repressor, Biology, medicine.disease_cause, Biochemistry, Epigenesis, Genetic, 03 medical and health sciences, chemistry.chemical_compound, Cytosine, 0302 clinical medicine, Cell Line, Tumor, medicine, Humans, Epigenetics, Nuclear protein, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Zinc finger, 5-Hydroxymethylcytosine, 0303 health sciences, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Cell Biology, DNA, Neoplasm, DNA Methylation, [CHIM.ORGA] Chemical Sciences/Organic chemistry, 3. Good health, Repressor Proteins, chemistry, 030220 oncology & carcinogenesis, 5-Methylcytosine, CpG Islands, Carcinogenesis, DNA, HeLa Cells, Protein Binding
Abstract

Recent studies have demonstrated that the modified base 5-hydroxymethylcytosine (5-hmC) is detectable at various rates in DNA extracted from human tissues. This oxidative product of 5-methylcytosine (5-mC) constitutes a new and important actor of epigenetic mechanisms. We designed a DNA pull down assay to trap and identify nuclear proteins bound to 5-hmC and/or 5-mC. We applied this strategy to three cancerous cell lines (HeLa, SH-SY5Y and UT7-MPL) in which we also measured 5-mC and 5-hmC levels by HPLC-MS/MS. We found that the putative oncoprotein Zinc finger and BTB domain-containing protein 2 (ZBTB2) is associated with methylated DNA sequences and that this interaction is inhibited by the presence of 5-hmC replacing 5-mC. As published data mention ZBTB2 recognition of p21 regulating sequences, we verified that this sequence specific binding was also alleviated by 5-hmC. ZBTB2 being considered as a multifunctional cell proliferation activator, notably through p21 repression, this work points out new epigenetic processes potentially involved in carcinogenesis.

Published
2014

23. TtcA a new tRNA-thioltransferase with an Fe-S cluster

Author

Jean-Luc Ravanat, Natty Labessan, Martin Clémancey, Mohamed G. Atta, Jean-Marc Latour, Marc Fontecave, Denis Bouvier, 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]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), 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), Chaire Chimie des processus biologiques, Laboratoire de Chimie des Processus Biologiques (LCPB), Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-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), Collège de France - Chaire Chimie des processus biologiques, Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Laboratoire Lésions des Acides Nucléiques (LAN), 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), Collège de France (CDF), and Collège de France (CdF)

Subjects
Iron-Sulfur Proteins, Dimer, Sulfurtransferase, Gene Expression, Biology, medicine.disease_cause, chemistry.chemical_compound, Genetics, medicine, Escherichia coli, [CHIM]Chemical Sciences, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Cysteine, Cloning, Molecular, Glutaredoxins, chemistry.chemical_classification, Nucleic Acid Enzymes, Escherichia coli Proteins, Mutagenesis, Enzyme, chemistry, Biochemistry, Sulfurtransferases, Transfer RNA, Cytosine
Abstract

International audience; TtcA catalyzes the post-transcriptional thiolation of cytosine 32 in some tRNAs. The enzyme from Es-cherichia coli was homologously overexpressed in E. coli. The purified enzyme is a dimer containing an iron–sulfur cluster and displays activity in in vitro assays. The type and properties of the cluster were investigated using a combination of UV-visible absorption , EPR and M ¨ ossbauer spectroscopy, as well as by site-directed mutagenesis. These studies demonstrated that the TtcA enzyme contains a redox-active and oxygen-sensitive [4Fe-4S] cluster, chelated by only three cysteine residues and absolutely essential for activity. TtcA is unique tRNA-thiolating enzyme using an iron–sulfur cluster for catalyzing a non-redox reaction.

Published
2014
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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
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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
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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
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27. Novel properties of melanins include promotion of DNA strand breaks, impairment of repair, and reduced ability to damage DNA after quenching of singlet oxygen

Author

Glaucia Regina Martinez, Andréia Akemi Suzukawa, Ana Maria da Costa Ferreira, Paolo Di Mascio, Daniela de Luna Martins, Alessandra Vieira, Jean-Luc Ravanat, Alexsandra Cristina Scalfo, Sheila M.B. Winnischofer, and Maria Eliane Merlin Rocha

Subjects
DNA Repair, DNA repair, DNA damage, medicine.medical_treatment, Free radicals, Photodynamic therapy, Biochemistry, Scavenger, Melanin, chemistry.chemical_compound, Physiology (medical), medicine, Melanins, Quenching (fluorescence), integumentary system, Singlet Oxygen, Singlet oxygen, Melanoma, Electron Spin Resonance Spectroscopy, medicine.disease, DNA minor groove binder, chemistry, Ferritins, Biophysics, DNA, DNA Damage
Abstract

Melanins have been associated with the development of melanoma and its resistance to photodynamic therapy (PDT). Singlet molecular oxygen (1O2), which is produced by ultraviolet A solar radiation and the PDT system, is also involved. Here, we investigated the effects that these factors have on DNA damage and repair. Our results show that both types of melanin (eumelanin and pheomelanin) lead to DNA breakage in the absence of light irradiation and that eumelanin is more harmful than pheomelanin. Interestingly, melanins were found to bind to the minor grooves of DNA, guaranteeing close proximity to DNA and potentially causing the observed high levels of strand breaks. We also show that the interaction of melanins with DNA can impair the access of repair enzymes to lesions, contributing to the perpetuation of DNA damage. Moreover, we found that after melanins interact with 1O2, they exhibit a lower ability to induce DNA breakage; we propose that these effects are due to modifications of their structure. Together, our data highlight the different modes of action of the two types of melanin. Our results may have profound implications for cellular redox homeostasis, under conditions of induced melanin synthesis and irradiation with solar light. These results may also be applied to the development of protocols to sensitize melanoma cells to PDT.

Published
2011

28. Extranuclear protection of chromosomal DNA from oxidative stress

Author

Vladimir Shulaev, Frank Van Breusegem, Gad Miller, Nobuhiro Suzuki, Stijn Morsa, Marc Van Montagu, Jean-Luc Ravanat, Christian Triantaphylidès, Alicia Hegie, Brigitte van de Cotte, Sandy Vanderauwera, Ron Mittler, 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
0106 biological sciences, Programmed cell death, Cytoplasm, DNA, Plant, DNA damage, Immunoblotting, Arabidopsis, Cell Cycle Proteins, Protein Serine-Threonine Kinases, medicine.disease_cause, 01 natural sciences, Chromosomes, Plant, 03 medical and health sciences, chemistry.chemical_compound, Ascorbate Peroxidases, Gene Expression Regulation, Plant, medicine, Cluster Analysis, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Oligonucleotide Array Sequence Analysis, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, Mutation, Multidisciplinary, biology, Arabidopsis Proteins, Reverse Transcriptase Polymerase Chain Reaction, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Gene Expression Profiling, Gene Expression Regulation, Developmental, Hydrogen Peroxide, Biological Sciences, Oxidants, Nuclear DNA, Oxidative Stress, Biochemistry, chemistry, Peroxidases, Catalase, biology.protein, Reactive Oxygen Species, DNA, Oxidative stress, 010606 plant biology & botany, DNA Damage
Abstract

Eukaryotic organisms evolved under aerobic conditions subjecting nuclear DNA to damage provoked by reactive oxygen species (ROS). Although ROS are thought to be a major cause of DNA damage, little is known about the molecular mechanisms protecting nuclear DNA from oxidative stress. Here we show that protection of nuclear DNA in plants requires a coordinated function of ROS-scavenging pathways residing in the cytosol and peroxisomes, demonstrating that nuclear ROS scavengers such as peroxiredoxin and glutathione are insufficient to safeguard DNA integrity. Both catalase (CAT2) and cytosolic ascorbate peroxidase (APX1) play a key role in protecting the plant genome against photorespiratory-dependent H 2 O 2 -induced DNA damage. In apx1/cat2 double-mutant plants, a DNA damage response is activated, suppressing growth via a WEE1 kinase-dependent cell-cycle checkpoint. This response is correlated with enhanced tolerance to oxidative stress, DNA stress-causing agents, and inhibited programmed cell death.

Published
2011
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29. First Steps Towards an Understanding of a Mode of Carcinogenic Action for Vanadium Pentoxide

Author

Detlef Schuler, Marc Walter, Jean-Luc Ravanat, Hans-Jörg Chevalier, Katja Morgenthal, Klaus Weber, Peter Sagelsdorff, Douglas McGregor, Mandy Merker, 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
Pathology, medicine.medical_specialty, Original, Vanadium, chemistry.chemical_element, 010501 environmental sciences, Toxicology, medicine.disease_cause, 01 natural sciences, Pathology and Forensic Medicine, 03 medical and health sciences, chemistry.chemical_compound, comet assay, medicine, Pentoxide, oxidative stress, mouse inhalation, Mode of action, Carcinogen, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, Inhalation, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Glutathione, respiratory system, vanadium pentoxide, Molecular biology, 3. Good health, DNA lesions, Comet assay, chemistry, Oxidative stress
Abstract

Inhalation of vanadium pentoxide clearly increases the incidence of alveolar/bronchiolar neoplasms in male and female B6C3F1 mice at all concentrations tested (1, 2 or 4 mg/m(3)), whereas responses in F344/N rats was, at most, ambiguous. While vanadium pentoxide is mutagenic in vitro and possibly in vivo in mice, this does not explain the species or site specificity of the neoplastic response. A nose-only inhalation study was conducted in female B6C3F1 mice (0, 0.25, 1 and 4 mg/m(3), 6 h/day for 16 days) to explore histopathological, biochemical (α-tocopherol, glutathione and F2-isoprostane) and genetic (comet assays and 9 specific DNA-oxo-adducts) changes in the lungs. No treatment related histopathology was observed at 0.25 mg/m(3). At 1 and 4 mg/m(3), exposure-dependent increases were observed in lung weight, alveolar histiocytosis, sub-acute alveolitis and/or granulocytic infiltration and a generally time-dependent increased cell proliferation rate of histiocytes. Glutathione was slightly increased, whereas there were no consistent changes in α-tocopherol or 8-isoprostane F2α. There was no evidence for DNA strand breakage in lung or BAL cells, but there was an increase in 8-oxodGuo DNA lesions that could have been due to vanadium pentoxide induction of the lesions or inhibition of repair of spontaneous lesions. Thus, earlier reports of histopathological changes in the lungs after inhalation of vanadium pentoxide were confirmed, but no evidence has yet emerged for a genotoxic mode of action. Evidence is weak for oxidative stress playing any role in lung carcinogenesis at the lowest effective concentrations of vanadium pentoxide.

Published
2011
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30. Measurement of oxidatively generated base damage in cellular DNA

Author

Thierry Douki, Jean-Luc Ravanat, Jean Cadet, 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), 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, DNA damage, DNA repair, Health, Toxicology and Mutagenesis, medicine.disease_cause, Nucleobase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Genetics, medicine, Humans, Molecular Biology, Chromatography, High Pressure Liquid, Enzyme Assays, 030304 developmental biology, Chromatography, 0303 health sciences, DNA extraction, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Oxidative Stress, Biochemistry, chemistry, DNA glycosylase, 030220 oncology & carcinogenesis, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Nucleic acid, DNA, Oxidative stress, DNA Damage
Abstract

This survey focuses on the critical evaluation of the main methods that are currently available for monitoring single and complex oxidatively generated damage to cellular DNA. Among chromatographic methods, HPLC-ESI-MS/MS and to a lesser extent HPLC-ECD which is restricted to a few electroactive nucleobases and nucleosides are appropriate for measuring the formation of single and clustered DNA lesions. Such methods that require optimized protocols for DNA extraction and digestion are sensitive enough for measuring base lesions formed under conditions of severe oxidative stress including exposure to ionizing radiation, UVA light and high intensity UVC laser pulses. In contrast application of GC-MS and HPLC-MS methods that are subject to major drawbacks have been shown to lead to overestimated values of DNA damage. Enzymatic methods that are based on the use of DNA repair glycosylases in order to convert oxidized bases into strand breaks are suitable, even if they are far less specific than HPLC methods, to deal with low levels of single modifications. Several other methods including immunoassays and (32)P-postlabeling methods that are still used suffer from drawbacks and therefore are not recommended. Another difficult topic is the measurement of oxidatively generated clustered DNA lesions that is currently achieved using enzymatic approaches and that would necessitate further investigations.

Published
2011

31. Excision of 7,8-dihydro-8-oxoguanine from DNA by the Fpg protein

Author

Jean-Luc Ravanat, J. Laval, S. Boiteux, Jean Cadet, and M. Berger

Subjects
chemistry.chemical_classification, Fpg protein, biology, medicine.disease_cause, biology.organism_classification, Biochemistry, Enterobacteriaceae, 8-Oxoguanine, chemistry.chemical_compound, Enzyme, chemistry, DNA glycosylase, medicine, Escherichia coli, DNA, Bacteria
Abstract

La chromatographie liquide haute performance couplee avec une detection amperometrique a ete utilisee afin de mettre en evidence la formation de la 7,8-dihydro-8-oxoguanine dans l'ADN photosensibilise par le bleu de methylene. La mesure de la base oxydee a ete effectuee apres hydrolyse acide de la macromolecule d'ADN. L'utilisation de cette methode nous a permis de montrer que l'incubation de l'ADN irradie en presence de la proteine Fpg conduit a l'excision quasi-quantitative de la 7,8-dihydro-8-oxoguanine

Published
1993
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32. 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
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33. Interference between nanoparticles and metal homeostasis

Author

Jean-Marc Moulis, Thierry Rabilloud, Patrice Catty, Jean-Luc Ravanat, Véronique Collin-Faure, Serge M. Candéias, A. Petit, P Charbonnier, Martine Cuillel, Sylvie Luche, Elisabeth Mintz, Nathalie Herlin-Boime, Isabelle Michaud-Soret, Marie Carrière, Axelle Casanova, S Ollagnier de Choudens, Cécile Lelong, C Aude Garcia, V Nivière, Thierry Douki, Sylvie Sauvaigo, Mireille Chevallet, 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), Biochimie et biophysique des systèmes intégrés (BBSI), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire Francis PERRIN (LFP - URA 2453), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-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 Structure et Dynamique par Résonance Magnétique (LCF) (LSDRM), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Joseph Fourier - Grenoble 1 (UJF)-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 Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-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), 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]), 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
History, Materials science, DNA damage, Nanoparticle, 010501 environmental sciences, medicine.disease_cause, 01 natural sciences, Education, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, medicine, 030304 developmental biology, 0105 earth and related environmental sciences, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, 89.60.Gg, # 87.85.Qr, # 87.14.Cc, 87.14.G, 89.60.Ec, 61.46.Df, technology, industry, and agriculture, Computer Science Applications, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Biochemistry, chemistry, Toxicity, Oxidative stress, Genotoxicity, Homeostasis
Abstract

International audience; The TiO2 nanoparticles (NPs) are now produced abundantly and widely used in a variety of consumer products. Due to the important increase in the production of TiO2-NPs, potential widespread exposure of humans and environment may occur during both the manufacturing process and final use. Therefore, the potential toxicity of TiO2-NPs on human health and environment has attracted particular attention. Unfortunately, the results of the large number of studies on the toxicity of TiO2-NPs differ significantly, mainly due to an incomplete characterization of the used nanomaterials in terms of size, shape and crystalline structure and to their unknown state of agglomeration/aggregation. The purpose of our project entitled NanoBioMet is to investigate if interferences between nanoparticles and metal homeostasis could be observed and to study the toxicity mechanisms of TiO2-NPs with well-characterized physicochemical parameters, using proteomic and molecular approaches. A perturbation of metal homeostasis will be evaluated upon TiO2-NPs exposure which could generate reactive oxygen species (ROS) production. Moreover, oxidative stress consequences such as DNA damage and lipid peroxidation will be studied. The toxicity of TiO2-NPs of different sizes and crystalline structures will be evaluated both in prokaryotic (E. coli) and eukaryotic cells (A549 human pneumocytes, macrophages, and hepatocytes). First results of the project will be presented concerning the dispersion of TiO2-NPs in bacterial medium, proteomic studies on total extracts of macrophages and genotoxicity on pneumocytes.

Published
2010
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34. 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
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35. Relative contribution of DNA strand breaks and DNA adducts to the genotoxicity of benzo[a]pyrene as a pure compound and in complex mixtures

Author

Emmanuel Lefèbvre, Jean-Luc Ravanat, Adeline Tarantini, Anne Maitre, Marie Marques, Thierry Douki, Caroline Marie, 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), EPSP, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), 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), Centre Hospitalier Universitaire [Grenoble] (CHU), 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, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble, 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), 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 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
DNA damage, Health, Toxicology and Mutagenesis, Metabolite, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Complex Mixtures, 010501 environmental sciences, medicine.disease_cause, 01 natural sciences, Cell Line, Adduct, Toxicology, DNA Adducts, 03 medical and health sciences, chemistry.chemical_compound, Occupational Exposure, Benzo(a)pyrene, Genetics, medicine, Humans, Molecular Biology, Carcinogen, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, Chromatography, Dose-Response Relationship, Drug, Hep G2 Cells, Comet assay, Oxidative Stress, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Pyrene, Particulate Matter, Genotoxicity, DNA Damage, Mutagens
Abstract

Polycyclic aromatic hydrocarbons (PAH) produced upon incomplete combustion of organic matter are suspected to be carcinogenic to humans. In the present work, we especially studied the genotoxicity of benzo[a]pyrene (B[a]P), pure or in mixtures, with emphasis placed on the contribution of oxidative stress and alkylation. A comparison was made between the extent of DNA strand breaks as determined by the Comet assay and the number of DNA adducts to the diol epoxide metabolite of B[a]P measured by HPLC-mass spectrometry. HepG2 cultured human hepatocytes were treated with either pure B[a]P or particulate matter extracted from air samples collected in an urban peri-industrial site or in a metallurgic plant. Treatment with pure B[a]P did not induce increase in Comet measurements below a concentration of 1 microM whereas adducts were observed for concentrations as low as 0.025 microM. Very different results were obtained with environmental samples. Increase in the Comet score was observed with both urban and industrial mixtures containing 0.16 microM of B[a]P, especially for samples of urban origin. Comparison with the effect of the reconstituted PAH fraction of the mixtures allowed us to conclude that the induction of strand breaks results from the action of other components of the samples. In addition, a 30% potentialization and a 90% inhibition in the level of DNA adducts with respect to exposure to 0.16 microM pure B[a]P were observed for cells exposed to industrial and urban mixtures, respectively. These results contrast with the 6-fold enhancement in the yield of BPDE adducts in cells exposed to the reconstituted PAH fraction with respect to pure BaP. Altogether, our data emphasize that (i) a combination of analytical approaches is required to assess the genotoxicity of complex mixtures and (ii) risk assessment based on additivity consideration such as toxic equivalent factors may be misleading.

Published
2009
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36. Protective effects of antioxidants against UVA-induced DNA damage in human skin fibroblasts in culture

Author

Jean-Luc Ravanat, Marie-Jeanne Richard, J. C. Beani, J. Cadet, Nathalie Emonet-Piccardi, N Signorini, 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
Adult, Antioxidant, Ultraviolet Rays, DNA damage, medicine.medical_treatment, chemistry.chemical_element, Human skin, Biochemistry, Antioxidants, 03 medical and health sciences, chemistry.chemical_compound, Sodium Selenite, 0302 clinical medicine, Chlorides, medicine, Humans, Breast, Cytotoxicity, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Skin, 030304 developmental biology, Electrophoresis, Agar Gel, Gel electrophoresis, 0303 health sciences, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, General Medicine, Fibroblasts, Molecular biology, Acetylcysteine, 3. Good health, Comet assay, Zinc Compounds, 030220 oncology & carcinogenesis, Agarose, Female, sense organs, Selenium, DNA Damage
Abstract

Ultraviolet A radiation (UVA, 320-400 nm) is mutagenic and induces genomic damage to skin cells. N-acetyl-cysteine (NAC), selenium and zinc have been shown to have antioxidant properties and to exhibit protective effects against UVA cytotoxicity. The present work attempts to delineate the effect of these compounds on genomic integrity of human skin fibroblasts exposed to UVA radiation using the single cell gel electrophoresis (SCGE) or Comet assay. The cells were incubated with NAC (5 mM), sodium selenite (0.6 microM) or zinc chloride (100 microM). Then cells were embedded in low melting point agarose, and immediately submitted to UVA fluences ranging from 1 to 6J/cm2. In the Comet assay, the tail moment increased by 45% (1 J/cm2) to 89% (6J/cm2) in non-supplemented cells (p)

Published
2009
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37. Urinary levels of oxidative DNA and RNA damage among workers exposed to polycyclic aromatic hydrocarbons in silicon production: Comparison with 1-hydroxypyrene

Author

Franck Balducci, Carine Badouard, Anne Maitre, Jean-Luc Ravanat, Marie Marques, Caroline Marie, 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
Adult, Male, Silicon, Epidemiology, Health, Toxicology and Mutagenesis, Population, Oxidative phosphorylation, Urine, 010501 environmental sciences, medicine.disease_cause, 01 natural sciences, Toxicology, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, Occupational Exposure, medicine, Humans, Deoxyguanosine, Polycyclic Aromatic Hydrocarbons, education, Chromatography, High Pressure Liquid, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0105 earth and related environmental sciences, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, education.field_of_study, Pyrenes, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Metabolism, Middle Aged, Oxidative Stress, chemistry, Biochemistry, 8-Hydroxy-2'-Deoxyguanosine, 13. Climate action, Chemical Industry, RNA, Biomarkers, DNA, Oxidative stress, DNA Damage
Abstract

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous occupational and environmental pollutants and the urinary excretion of 1-hydroxypyrene (1-OHP) is classically measured for the determination of PAH exposure internal dose. Some of PAH are tumorigenic due to their metabolites ability to generate DNA adducts and oxidative DNA damage through the production of reactive oxygen species during metabolism. 8-hydroxy-7,8-dihydro-2'-deoxyguanosine (8-OHdGuo) is one of the major oxidative DNA lesions and its use as a potential biomarker of genotoxic PAH occupational exposure should be evaluated. Indeed conflicting results are frequently reported in occupational studies in terms of correlation between 8-OHdGuo urinary levels and PAH exposure. The aim of our study was therefore to determine the potential for PAH occupational exposure to increase urinary oxidative DNA damage. The population consisted of 68 male workers employed in silicon production. The urinary concentrations of 8-OHdGuo and its homologue in RNA, 8-hydroxy-7,8-dihydroguanosine (8-OHGuo) were determined using high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry, whereas those of 1-OHP were measured using HPLC with fluorescence detection. Individual variation rates were calculated on a working day and a working week. The results indicated that, while 1-OHP levels strongly increased on a working day and even more on a working week, 8-OHdGuo and 8-OHGuo urinary levels did not show similar significant increases. Moreover, no correlation between 1-OHP and oxidative DNA and RNA lesions was found. Consequently, urinary 8-OHdGuo and 8-OHGuo did not seem to be relevant biomarkers of genotoxic PAH exposure in the case of the silicon plant studied.

Published
2009
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38. A microarray to measure repair of damaged plasmids by cell lysates

Author

Guillaume Arras, C. Claudet, Sylvie Sauvaigo, C. Dumontet, Alain Sarasin, A.-L. Raffin, Thierry Oddos, A. Favier, Jean-Luc Ravanat, S. Chevillard, Thierry Douki, J.-F. Millau, Jean Breton, N. Ugolin, Sylvain Caillat, 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), Laboratoire de Physique et Technologies des Plasmas (LPTP), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Génomes et cancer (GC (FRE2939)), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Etude des relations instabilité génétique et cancer (ERIGC), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Cancérologie Expérimentale (LCE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, 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
Xeroderma pigmentosum, Microarray, DNA Repair, DNA repair, Biomedical Engineering, Bioengineering, Biology, Biochemistry, Peripheral blood mononuclear cell, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Plasmid, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, Humans, 030304 developmental biology, Cell Line, Transformed, 0303 health sciences, General Chemistry, medicine.disease, Molecular biology, Phenotype, Spectrometry, Fluorescence, chemistry, 030220 oncology & carcinogenesis, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Cancer biomarkers, DNA, HeLa Cells, Plasmids
Abstract

DNA repair mechanisms constitute major defences against agents that cause cancer, degenerative disease and aging. Different repair systems cooperate to maintain the integrity of genetic information. Investigations of DNA repair involvement in human pathology require an efficient tool that takes into account the variety and complexity of repair systems. We have developed a highly sensitive damaged plasmid microarray to quantify cell lysate excision/synthesis (ES) capacities using small amounts of proteins. This microsystem is based on efficient immobilization and conservation on hydrogel coated glass slides of plasmid DNA damaged with a panel of genotoxic agents. Fluorescent signals are generated from incorporation of labelled dNTPs by DNA excision-repair synthesis mechanisms at plasmid sites. Highly precise DNA repair phenotypes i.e. simultaneous quantitative measures of ES capacities toward seven lesions repaired by distinct repair pathways, are obtained. Applied to the characterization of xeroderma pigmentosum (XP) cells at basal level and in response to a low dose of UVB irradiation, the assay showed the multifunctional role of different XP proteins in cell protection against all types of damage. On the other hand, measurement of the ES of peripheral blood mononuclear cells from six donors revealed significant diversity between individuals. Our results illustrate the power of such a parallelized approach with high potential for several applications including the discovery of new cancer biomarkers and the screening of chemical agents modulating DNA repair systems.

Published
2008

39. 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
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40. Determination of new types of DNA lesions in human sperm

Author

Gilles Panteix, Yves Menezo, A. Favier, Jean-Luc Ravanat, Jean Cadet, Thierry Douki, 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
Male, Adenosine, DNA damage, medicine.medical_treatment, Biology, medicine.disease_cause, Mass Spectrometry, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, DNA Adducts, 0302 clinical medicine, Human fertilization, medicine, Humans, Chromatography, High Pressure Liquid, 030304 developmental biology, 0303 health sciences, 030219 obstetrics & reproductive medicine, Assisted reproductive technology, Guanosine, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 8-Hydroxy-2'-deoxyguanosine, Deoxyguanosine, Cell Biology, Sperm, Spermatozoa, 3. Good health, Oxidative Stress, Biochemistry, chemistry, 8-Hydroxy-2'-Deoxyguanosine, Oxidative stress, DNA, Developmental Biology, DNA Damage
Abstract

SummaryCareful attention has been focused recently on DNA quality in human IVF. Therefore a variety of methods has been developed to evaluate DNA integrity, especially concerning fragmentation. Using liquid chromatography and mass spectrometry (LC/MS/MS) for our best sperm samples, we have established reference values for several oxidative lesions, in order to gain insights into the cause of DNA lesions. Besides 8-oxodeoxyguanosine, we found rather high levels of two ethenonucleosides: 1,N6-ethenoadenosine and 1,N2-ethenoguanosine. These compounds probably arise from a reaction with 4-hydroxy-2-nonenal, the main aldehyde compound released during lipid peroxidation, or after occupational exposure to vinyl chloride. The quantity of chlorinated bases detected is low. All of this decay has to be repaired by the oocytes at the time of fertilization or immediately after. This aspect should not be overlooked in assisted reproductive technology, in order to understand risks and limitations.

Published
2008
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41. 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

42. Heavy-atom enhanced synchrotron stereotactic radiotherapy of brain tumors: from DNA to preclinical studies

Author

L. Bobyk, J. Rousseau, Hélène Elleaume, and Jean-Luc Ravanat

Subjects
Cisplatin, Oncology, Chemotherapy, medicine.medical_specialty, Renewable Energy, Sustainability and the Environment, Health, Toxicology and Mutagenesis, medicine.medical_treatment, Public Health, Environmental and Occupational Health, medicine.disease, Carboplatin, Oxaliplatin, Radiation therapy, chemistry.chemical_compound, Nuclear Energy and Engineering, chemistry, In vivo, Concomitant, Internal medicine, Glioma, medicine, Safety, Risk, Reliability and Quality, Waste Management and Disposal, medicine.drug
Abstract

Gliomas are the most frequent primary brain tumors in adults. Despite multimodality treatment strategies that combine surgery, chemotherapy and radiotherapy, high grade gliomas are almost uniformly fatal. Heavy-atom-enhanced synchrotron stereotactic radiotherapy (SSR) is a novel therapeutic modality proposed to increase the toxicity to the tumor while protecting the surrounding healthy tissue. It consists in selective accumulation of high-Z elements in tumor followed by stereotactic irradiation, in tomography mode, with monochromatic X-rays from a synchrotron source, tuned at an optimal energy. Two complimentary SSR approaches have been successfully developed in the past 5 years, and may be promising in high-grade glioma management: iodine-enhanced SSR , with an iodinated contrast agent; and Pt-enhanced SSR , , a concomitant radio-chemotherapy treatment with locoregional injection of platinated chemotherapy drugs. Several in vitro and in vivo experiments have been carried out at the European Synchrotron Radiation Facility, either with iodine or platinum. In vivo experiments are performed on F98 glioma-bearing rats. The F98 glioma model simulates several characteristics of human glioblastoma including lethality following treatment with a variety of therapeutic modalities. Recently, we have shown that a significant increase in survival time is obtained when the platinated drug (cisplatin or carboplatin) is infused intratumoraly followed by X-rays irradiation. Furthermore, a significant percent of animals are cured. To optimise the treatment, work is in progress in order to determine and increase the incorporation of heavy-atoms in tumoral cells and also to improve the intracerebral drug distribution by developing new injection methods and using different chemotherapeutic drugs including oxaliplatin, chlorotertpyridineplatinum and 5-iodo-2’-deoxyuridine. In addition, efforts will be made to have a better understanding of the biological consequences at the molecular and cellular level of the SSR treatment. 1 - Adam JF et al, International Journal of Radiation Oncology, Biology, Physics 2006; 64:603-611. 2 Biston MC et al, Cancer Research 2004; 64:2317-2323. 3 Rousseau J et al, Clinical Cancer Research 2007;13:5195-5201.

Published
2008
Full Text
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43. Influence of a static magnetic field (250 mT) on the antioxidant response and DNA integrity in THP1 cells

Author

Jean-Luc Ravanat, Thery Douki, Mohsen Sakly, Salem Amara, Catherine Garrel, Hafedh Abdelmelek, Pascale Guiraud, Alain Favier, Khémais Ben Rhouma, 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)-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), Unité de Biochimie Hormonale et Nutritionnelle, Biologie-Toxicologie-pharmacologie, Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire ORSOX, Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Physiologie Animale, Faculté des Sciences de Bizerte [Université de Carthage], Université de Carthage - University of Carthage-Université de Carthage - University of Carthage, 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 Centre Hospitalier Universitaire de Grenoble

Subjects
[CHIM.ANAL] Chemical Sciences/Analytical chemistry, DNA damage, medicine.disease_cause, Antioxidants, Superoxide dismutase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Electromagnetic Fields, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Malondialdehyde, medicine, Tumor Cells, Cultured, Humans, Radiology, Nuclear Medicine and imaging, DNA Breaks, Single-Stranded, Chromatography, High Pressure Liquid, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Glutathione Peroxidase, Radiological and Ultrasound Technology, biology, Superoxide Dismutase, Glutathione peroxidase, Dose-Response Relationship, Radiation, Catalase, Fluoresceins, Molecular biology, Comet assay, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Dose–response relationship, chemistry, 030220 oncology & carcinogenesis, [SDV.TOX]Life Sciences [q-bio]/Toxicology, biology.protein, Leukocytes, Mononuclear, Comet Assay, Oxidative stress
Abstract

The aim of this study was to investigate the effect of static magnetic field (SMF) exposure in antioxidant enzyme activity, the labile zinc fraction and DNA damage in THP1 cells (monocyte line). Cell culture flasks were exposed to SMF (250 mT) during 1 h (group 1), 2 h (group 2) and 3 h (group 3). Our results showed that cell viability was slightly lower in SMF-exposed groups compared to a sham exposed group. However, SMF exposure failed to alter malondialdehyde (MDA) concentration (+6%, p>0.05) and glutathione peroxidase (GPx) (-5%, p>0.05), catalase (CAT) (-6%, p>0.05) and superoxide dismutase (SOD) activities (+38%, p>0.05) in group 3 compared to the sham exposed group. DNA analysis by single cell gel electrophoresis (comet assay) revealed that SMF exposure did not exert any DNA damage in groups 1 and 2. However, it induced a low level of DNA single strand breaks in cells of group 3. To further explore the oxidative DNA damage, cellular DNA for group 3 was isolated, hydrolyzed and analysed by HPLC-EC. The level of 8-oxodGuo in this group remained unchanged compared to the sham exposed group (+6.5%, p>0.05). Cells stained with zinc-specific fluorescent probes zinpyr-1 showed a decrease of labile zinc fraction in all groups exposed to SMF. Our data showed that SMF exposure (250 mT, during 3 h) did not cause oxidative stress and DNA damage in THP1 cells. However, SMF could alter the intracellular labile zinc fraction.

Published
2007

44. Zinc supplementation ameliorates static magnetic field-induced oxidative stress in rat tissues

Author

Salem Amara, Mohsen Sakly, Hafedh Abdelmelek, Jean-Luc Ravanat, Pascale Guiraud, Alain Favier, Catherine Garrel, 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
medicine.medical_specialty, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, Antioxidant, Health, Toxicology and Mutagenesis, medicine.medical_treatment, 010501 environmental sciences, Toxicology, medicine.disease_cause, 01 natural sciences, Lipid peroxidation, Superoxide dismutase, 03 medical and health sciences, chemistry.chemical_compound, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Internal medicine, medicine, 030304 developmental biology, 0105 earth and related environmental sciences, Pharmacology, chemistry.chemical_classification, 0303 health sciences, Kidney, biology, Glutathione peroxidase, General Medicine, Malondialdehyde, 3. Good health, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Endocrinology, medicine.anatomical_structure, chemistry, Biochemistry, Catalase, [SDV.TOX]Life Sciences [q-bio]/Toxicology, biology.protein, Oxidative stress
Abstract

The present study was undertaken to find out the effect of zinc supplementation on the antioxidant enzymatic system, lipid peroxidation and DNA oxidation in liver and kidney of static magnetic field (SMF) exposed rats. The exposure of rats to SMF (128 mT, 1 h/day during 30 consecutive days) decreased the activities of glutathione peroxidase (GPx), catalase (CAT) and the superoxide dismutase (SOD) in liver and kidney. By contrast, sub-chronic exposure to SMF increased the malondialdehyde (MDA) concentration in liver and kidney. Our results revealed an increase of the 8-oxo-7,8-dihydro-2′-desoxyguanosine (8-oxodGuo) in kidney of SMF-exposed rats. However, this biomarker of DNA oxidation remained unchanged in liver. Zinc supplementation (ZnCl 2 , 40 mg/l, per os ) in SMF-exposed rats restored the activities of GPx, CAT and SOD in liver to those of control group. However, only CAT activity was restored in kidney. Moreover, zinc administration was able to bring down the elevated levels of MDA in the liver but not in the kidney. Interestingly, zinc supplementation attenuated DNA oxidation induced by SMF in kidney to the control level. Our investigations suggested that zinc supplementation minimizes oxidative damage induced by SMF in rat tissues.

Published
2007

45. One-electron oxidation of DNA and inflammation processes

Author

Jean-Luc Ravanat, Jean Cadet, Thierry Douki, 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), Douki, Thierry, 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, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, Chemistry, Guanine, Inflammation, Cell Biology, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, 3. Good health, DNA metabolism, [SDV.TOX] Life Sciences [q-bio]/Toxicology, 03 medical and health sciences, Sequence selectivity, chemistry.chemical_compound, Biochemistry, Guanine metabolism, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, medicine, medicine.symptom, Molecular Biology, DNA, 030304 developmental biology
Abstract

Nitrosoperoxycarbonate anion, a reactive species generated in inflammation processes, is able to specifically oxidize guanine bases with a sequence selectivity that is almost opposite from that usually observed for one-electron oxidants.

Published
2006

46. 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

47. 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

48. From DNA Photolesions to Mutations, Skin Cancer and Cell Death

Author

Nathalie Bastien, Cecilia Becerril, Vyacheslav A Bespalov, Serge Boiteux, Ihor P Boszko, Douglas E Brash, Jean Cadet, Colleen Caney, K-John Cheung Jr, Antonio Conconi, Raphael M Culerrier, Jocelyn David, R Jeremy H Davies, Julie Desnoyers, Thierry Douki, Elliot Drobetsky, Jean-Claude Ehrhart, Deirdre Fahy, Murray A Francis, Fabien P Gosselet, Pal Grof, Dong-Hyun Lee, Caroline Leger, Gang Li, Geraldine Mathonnet, Bruce C McKay, Leon H F Mullenders, Dennis H Oh, Daniel Perdiz, Gerd P Pfeifer, Photini Pitsikas, Jean-Pierre Pouget, Andrew J Rainbow, Dindial Ramotar, Jean-Luc Ravanat, Anne Reynaud-Angelin, Patrick Rochette, Alain Sarasin, Girish M Shah Shah, Michael J Smerdon, Jennifer Spronck, Sharon M Starrs, Clarke S Stevenson, John-Stephen Taylor, and Momchil D Vodenicharov

Subjects
Programmed cell death, chemistry.chemical_compound, Chemistry, medicine, Cancer research, Skin cancer, medicine.disease, DNA
Abstract

As modern day society takes an increasing interest in outdoor activities, its exposure to sunlight has never been greater. As a consequence, countries throughout the world are experiencing a dramatic increase in the incidences of skin carcinomas and melanomas. From DNA photolesions to mutations, skin cancer and cell death provides an authoritative source of information for photobiologists interested in the series of genetic events that occur in the skin, and eventually lead to cancer. With contributions from eminent scientists in the field, this book includes the latest information on DNA photolesions and repair, as well as the key mechanisms of solar UV in skin cancer initiation and development. Significant information relating to UV-induced photolesions and mechanisms of skin tumour occurrence is also included. By providing the basic phenomena underlying the science and an overview of the biological events that take place when cells are exposed to solar UV radiation, From DNA photolesions to mutations, skin cancer and cell death is suitable to all researchers interested in the process of photocarcinogenesis.

Published
2005
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49. 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
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50. 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
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