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9 results on '"Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX)"'

1. The LILAS project: analysis of applying participatory approaches such as Living Labs to research on multiple environmental exposures to ionizing radiation, other stressors and chronic risks

Author

LAURENT, Olivier, Yara Carrejo, Gironza, Ancelet, Sophie, Armant, Olivier, Denis, Bard, Katia, Baumgartner, Sylvie, Bortoli, Boudet, Céline, Chamaret, Philippe, Chartier, Michel, Cormier, Stéphanie, Arthur, David, Desqueyroux, Hélène, Gerber, Mariette, Gilbin, Rodolphe, Grimbuhler, Sonia, Larqué, Lionel, Laurier, Dominique, Mougin, Christian, Gamet-Payrastre, Laurence, Rannou, Alain, Reaud, Cynthia, Scanff, Pascale, Vanzemberg, Arnaud, Schraub, Simon, Supervil, Sylvie, Eric, Thybaud, Trousse, Brigitte, Charron, Sylvie, Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Société francophone de santé environnement (SFSE), France Nature Environnement (FNE), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut Ecocitoyen pour la Connaissance des Pollutions [Fos-sur-Mer], Centre Permanent d'Initiatives pour l'Environnement des Pays de l'Aisne (CPIE des Pays de l'Aisne), École des Hautes Études en Santé Publique [EHESP] (EHESP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Association nationale des comités et commissions locales d'information [Teteghem] (ANCCLI), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Technologies et Méthodes pour les Agricultures de demain (UMR ITAP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), ALLISS Sciences Sociétés [Paris], Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pôle Santé Environnement - Direction Santé (IRSN/PSE-SANTE), Service des politiques d’ouverture à la société (IRSN/DST/SPOS), Direction de la Stratégie (IRSN/DST), Cellule Valorisation des données (IRSN/DTR/D3NSI/SVDDA/CVD), Direction Déléguée Développement numérique et aux systèmes d’information (IRSN/DTR/D3NSI), Service de la programmation, des partenariats, de la prospective et de l’appui à l’innovation (IRSN/DST/SP3IN), Ligue Nationale Contre le Cancer (LNCC), Direction des Risques et de la Performance (IRSN/DRP), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), IRSN2030, ICRP - International Commission on Radiation Protection, Université de Rennes (UR), Département des sciences en santé environnementale (DEESSE), Laboratoire d'étude et de recherche en environnement et santé (LERES), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Protection et Sûreté Nucléaire (IPSN), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), IRSN via appel à projets interne IRSN2030, TECNICO LISBOA, and Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan)

Subjects
[SDE]Environmental Sciences, [SDE.ES]Environmental Sciences/Environmental and Society
Abstract

International audience; Participatory research approaches in environmental health are still rarely applied to radiation research. Opportunities for greater implication of the civil society and related challenges differ at each step of such research activities. The LILAS project aimed, as a preparatory step toward the development of participatory research projects on multiple environmental exposures to ionizing radiation and other stressors

Published
2022

2. DNA damage induced by Strontium-90 exposure at low concentrations in mesenchymal stromal cells: the functional consequences

Author

C. Grand, Stefania Musilli, N. Nicolas, Saadia Kerdine-Römer, Jean-Marc Bertho, P. Orellana-Moreno, Z. El Ali, Karine Tack, Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Radioprotection et de SÃreté Nucléaire, IRSN D3-P8-05-01, and ATHENA, Irsn

Subjects
0301 basic medicine, Senescence, Programmed cell death, Stromal cell, DNA Repair, DNA damage, DNA repair, [SDV]Life Sciences [q-bio], Article, Histones, 03 medical and health sciences, chemistry.chemical_compound, medicine, Animals, Humans, DNA Breaks, Double-Stranded, Cellular Senescence, Cell Proliferation, Analysis of Variance, Multidisciplinary, Cell Death, Mesenchymal stem cell, Cell Differentiation, Mesenchymal Stem Cells, Cell biology, Rats, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, chemistry, Strontium Radioisotopes, Cytokines, Bone marrow, Reactive Oxygen Species, Oxidation-Reduction, DNA, DNA Damage
Abstract

90Sr is one of the radionuclides released after nuclear accidents that can significantly impact human health in the long term. 90Sr accumulates mostly in the bones of exposed populations. Previous research has shown that exposure induces changes in bone physiology both in humans and in mice. We hypothesize that, due to its close location with bone marrow stromal cells (BMSCs), 90Sr could induce functional damage to stromal cells that may explain these biological effects due to chronic exposure to 90Sr. The aim of this work was to verify this hypothesis through the use of an in vitro model of MS5 stromal cell lines exposed to 1 and 10 kBq.mL−1 of 90Sr. Results indicated that a 30-minute exposure to 90Sr induced double strand breaks in DNA, followed by DNA repair, senescence and differentiation. After 7 days of exposure, MS5 cells showed a decreased ability to proliferate, changes in cytokine expression, and changes in their ability to support hematopoietic progenitor proliferation and differentiation. These results demonstrate that chronic exposure to a low concentration of 90Sr can induce functional changes in BMSCs that in turn may explain the health effects observed in following chronic 90Sr exposure.

Published
2017
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3. Assessment of the Central Effects of Natural Uranium via Behavioural Performances and the Cerebrospinal Fluid Metabolome

Author

Maâmar Souidi, Karine Tack, Gaëlle Favé, B. Dhieux, Jean-Charles Martin, Christelle Elie, Stéphane Grison, Philippe Lestaevel, Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Radioprotection and Nuclear Safety (IRSN), Laboratoire de RadioToxicologie Expérimentale, Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lestaevel, Philippe, Institut de RadioProtection et de Sureté Nucléaire, Direction de la Radioprotection de l’Homme, Nutrition, obésité et risque thrombotique ( NORT ), Aix Marseille Université ( AMU ) -Institut National de la Recherche Agronomique ( INRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Institut de Radioprotection et de Sûreté Nucléaire ( IRSN/PRP-HOM/SRBE ), Institut de Radioprotection et de Sûreté Nucléaire ( IRSN ), and Laboratoire de radiotoxicologie expérimentale, Direction de la radioprotection de l'homme

Subjects
Male, 0301 basic medicine, hippocampus, Physiology, Spatial memory, Rats, Sprague-Dawley, Toxicology, chemistry.chemical_compound, stress, Cerebrospinal fluid, Lactation, Hippocampus (mythology), dose ionizing-radiation, Neurotransmitter, ComputingMilieux_MISCELLANEOUS, Cerebrospinal Fluid, Spatial Memory, Behavior, Animal, central-nervous-system, brain-development, sodium-butyrate, well water, exposure, rats, neurotransmitter, medicine.anatomical_structure, Neurology, Toxicity, Metabolome, Uranium, Female, Locomotion, Research Article, Article Subject, Central nervous system, Biology, lcsh:RC321-571, 03 medical and health sciences, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Maze Learning, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, [ SDV ] Life Sciences [q-bio], 030104 developmental biology, Animals, Newborn, chemistry, Neurology (clinical)
Abstract

Natural uranium (NU), a component of the earth’s crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NUvialactation and drinking water (1.5, 10, or 40 mg·L−1for male rats and 40 mg·L−1for female rats). Medium-term memory decreased in comparison to controls in male rats exposed to 1.5, 10, or 40 mg·L−1NU. In male rats, spatial working memory and anxiety- and depressive-like behaviour were only altered by exposure to 40 mg·L−1NU and any significant effect was observed on locomotor activity. In female rats exposed to NU, only locomotor activity was significantly increased in comparison with controls. LC-MS metabolomics of CSF discriminated the fingerprints of the male and/or female NU-exposed and control groups. This study suggests that exposure to environmental doses of NU from development to adulthood can have an impact on rat brain function.

Published
2016
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4. Metabolomics reveals dose effects of low-dose chronic exposure to uranium in rats: identification of candidate biomarkers in urine samples

Author

Matthieu Maillot, Isabelle Dublineau, Gaëlle Favé, Eric Blanchardon, Line Manens, Maâmar Souidi, Jean-Charles Martin, Olivia Delissen, Jocelyne Aigueperse, Stéphane Grison, Sandra Bohand, Institut de Radioprotection et de Sûreté Nucléaire (IRSN/PRP-HOM/SRBE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de RadioToxicologie Expérimentale, Laboratoire de radiotoxicologie expérimentale, Direction de la radioprotection de l'homme, Institut de RadioProtection et de Sureté Nucléaire, Direction de la Radioprotection de l’Homme, Département de Protection et de santé de l'Homme et de Dosimétrie, Section Autonome de Radiobiologie Appliquée à la Médecine (DPHD), AREVA, Groupe AREVA, Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle RadioProtection Homme (IRSN/PRP-HOM), and Royston Goodacre

Subjects
0301 basic medicine, Chronic exposure, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Physiology, chemistry.chemical_element, Urine, Biochemistry, Toxicology, 03 medical and health sciences, Metabolomics, Contamination, Dose effect, Chronic, N1-methylnicotinamide, Chemistry, Low dose, Uranium, Natural uranium, 3. Good health, 030104 developmental biology, Original Article
Abstract

Introduction Data are sparse about the potential health risks of chronic low-dose contamination of humans by uranium (natural or anthropogenic) in drinking water. Previous studies report some molecular imbalances but no clinical signs due to uranium intake. Objectives In a proof-of-principle study, we reported that metabolomics is an appropriate method for addressing this chronic low-dose exposure in a rat model (uranium dose: 40 mg L−1; duration: 9 months, n = 10). In the present study, our aim was to investigate the dose–effect pattern and identify additional potential biomarkers in urine samples. Methods Compared to our previous protocol, we doubled the number of rats per group (n = 20), added additional sampling time points (3 and 6 months) and included several lower doses of natural uranium (doses used: 40, 1.5, 0.15 and 0.015 mg L−1). LC–MS metabolomics was performed on urine samples and statistical analyses were made with SIMCA-P+ and R packages. Results The data confirmed our previous results and showed that discrimination was both dose and time related. Uranium exposure was revealed in rats contaminated for 9 months at a dose as low as 0.15 mg L−1. Eleven features, including the confidently identified N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide and 4-hydroxyphenylacetylglycine, discriminated control from contaminated rats with a specificity and a sensitivity ranging from 83 to 96 %, when combined into a composite score. Conclusion These findings show promise for the elucidation of underlying radiotoxicologic mechanisms and the design of a diagnostic test to assess exposure in urine, in a dose range experimentally estimated to be above a threshold between 0.015 and 0.15 mg L−1. Electronic supplementary material The online version of this article (doi:10.1007/s11306-016-1092-8) contains supplementary material, which is available to authorized users.

Published
2016
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5. Metabolomics identifies a biological response to chronic low-dose natural uranium contamination in urine samples

Author

Romain Bott, Line Manens, Nathalie Banzet, Gaëlle Favé, Stéphane Grison, Isabelle Dublineau, Catherine Defoort, Eric Blanchardon, Patrick Gourmelon, Maâmar Souidi, Jean-Charles Martin, Olivia Delissen, Jocelyne Aigueperse, Matthieu Maillot, PRP-HOM/SRBE/LRTOX, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Radioprotection et de Surete Nucleaire (IRSN), ProdInra, Migration, Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX), and Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Population, Low-dose, chemistry.chemical_element, Urine, 010501 environmental sciences, Pharmacology, 01 natural sciences, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Metabolomics, Medicine, Ingestion, Chronic, education, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, education.field_of_study, Nicotinamide, business.industry, Uranium, Natural uranium, Contamination, 3. Good health, [SDV] Life Sciences [q-bio], N-methylnicotinamide, chemistry, Original Article, business
Abstract

Because uranium is a natural element present in the earth’s crust, the population may be chronically exposed to low doses of it through drinking water. Additionally, the military and civil uses of uranium can also lead to environmental dispersion that can result in high or low doses of acute or chronic exposure. Recent experimental data suggest this might lead to relatively innocuous biological reactions. The aim of this study was to assess the biological changes in rats caused by ingestion of natural uranium in drinking water with a mean daily intake of 2.7 mg/kg for 9 months and to identify potential biomarkers related to such a contamination. Subsequently, we observed no pathology and standard clinical tests were unable to distinguish between treated and untreated animals. Conversely, LC–MS metabolomics identified urine as an appropriate biofluid for discriminating the experimental groups. Of the 1,376 features detected in urine, the most discriminant were metabolites involved in tryptophan, nicotinate, and nicotinamide metabolic pathways. In particular, N-methylnicotinamide, which was found at a level seven times higher in untreated than in contaminated rats, had the greatest discriminating power. These novel results establish a proof of principle for using metabolomics to address chronic low-dose uranium contamination. They open interesting perspectives for understanding the underlying biological mechanisms and designing a diagnostic test of exposure. Electronic supplementary material The online version of this article (doi:10.1007/s11306-013-0544-7) contains supplementary material, which is available to authorized users.

Published
2013
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6. Inhalation of uranium nanoparticles: respiratory tract deposition and translocation to secondary target organs in rats

Author

Isabelle Dublineau, Philippe Lestaevel, François Gensdarmes, Benjamin B. Tournier, B. Dhieux, F. Petitot, Sébastien Jacquinot, Patricia Beaunier, Charline Mazzucco, Olivia Delissen, Elie Tourlonias, Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Service du Confinement et de l'Aérodispersion des polluants (IRSN/PSN-RES/SCA), Laboratoire de Réactivité de Surface (LRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Radioprotection et de Sûreté Nucléaire (IRSN/PRP-HOM/SRBE), Laboratoire de radiotoxicologie expérimentale, Direction de la radioprotection de l'homme, and Institut de Radioprotection et de Sûreté Nucléaire (IRSN/PSN-RES/SCA)

Subjects
Nuclear fuel cycle, inorganic chemicals, Male, Respiratory System/drug effects/metabolism, Respiratory System, Metal Nanoparticles, chemistry.chemical_element, 010501 environmental sciences, Toxicology, 01 natural sciences, complex mixtures, Mass Spectrometry, Statistics, Nonparametric, Rats, Sprague-Dawley, 03 medical and health sciences, Microscopy, Electron, Transmission, Ultrafine particle, Depleted uranium, In vivo, Administration, Inhalation, medicine, Animals, Particle Size, 030304 developmental biology, 0105 earth and related environmental sciences, Inhalation exposure, 0303 health sciences, Inhalation, Chemistry, Radiochemistry, technology, industry, and agriculture, General Medicine, [CHIM.CATA]Chemical Sciences/Catalysis, Uranium, Uranium/pharmacokinetics/toxicity, Rats, Deposition (aerosol physics), medicine.anatomical_structure, Blood, Ultrafine particles, 13. Climate action, Nanoparticles, Rat, Respiratory tract, Metal Nanoparticles/toxicity
Abstract

International audience; Uranium nanoparticles (

Published
2013
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7. Different genotoxic profiles between depleted and enriched uranium

Author

Sandrine Frelon, M. De Meo, Isabelle Dublineau, F. Petitot, D. Broggio, A. Feugier, Carine Darolles, PRP-HOM/SRBE/LRTOX, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire d'évaluation de la dose interne (DRPH/SDI/LEDI), Biogénotoxicologie et Mutagenèse Environnementale (BME), Université de la Méditerranée - Aix-Marseille 2, Laboratoire de radiotoxicologie et radiobiologie expérimentale (LRTOX), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX), Laboratoire d'évaluation de la dose interne (IRSN/DRPH/SDI/LEDI), Service de Dosimétrie Interne (IRSN/DRPH/SDI), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), and Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE)

Subjects
Binucleated cells, [SDV]Life Sciences [q-bio], uranium 235, radiation exposure, animal cell, Toxicology, medicine.disease_cause, fibroblast, Mice, 0302 clinical medicine, Immunologic, Depleted uranium, Cells, Cultured, In Situ Hybridization, Fluorescence, In Situ Hybridization, Cytotoxicity Tests, 0303 health sciences, Mice, Inbred C3H, Cultured, Radiation, Micronucleus Tests, Cell Death, Chemistry, article, radiation carcinogenesis, risk assessment, General Medicine, Uranium, Inbred C3H, micronucleus test, priority journal, centromere, 030220 oncology & carcinogenesis, Micronucleus test, Uranium-235, Drug, ionizing radiation, Monte Carlo Method, Cell Division, Cells, chemistry.chemical_element, embryo, cytokinesis, Enriched uranium, complex mixtures, Fluorescence, Dose-Response Relationship, 03 medical and health sciences, medicine, Animals, controlled study, mouse, 030304 developmental biology, nonhuman, Dose-Response Relationship, Drug, concentration (parameters), Radiochemistry, genotoxicity, Dose-Response Relationship, Radiation, Cytotoxicity Tests, Immunologic, Micronucleus, Genotoxicity, Mutagens
Abstract

Uranium is an alpha-particle-emitting heavy metal. Its genotoxicity results from both its chemical and its radiological properties that vary with its isotopic composition (12% enriched uranium in 235U (EU) has a specific activity 20 times higher than 0.3% depleted uranium in 235U (DU)). The influence of the isotopic composition of uranium on its genotoxic profile (clastogenic/aneugenic) has never been described. The present study evaluated genotoxic profile of uranium with the cytokinesis-block micronucleus centromere assay. C3H10T1/2 mouse embryo fibroblasts were contaminated with either DU or EU at different concentrations (5 μM, 50 μM and 500 μM). Cells received low doses ranging from 0.3 μGy to 760.5 μGy. The frequency of binucleated cells with one micronucleus increased with increasing concentrations of both DU and EU in the same way. EU induced more centromere-negative micronuclei and nucleoplasmic bridges than DU. A correlation between these two clastogenic markers and ionizing radiation doses was observed. Finally, this study showed that the genotoxic profile of uranium depends on its isotopic composition. DU and EU are low and high clastogens, respectively. However, DU aneugenic effects remain high. Thus, there is a need to study the potential role of aneugenic effects of DU in carcinogenic risk assessment linked to uranium internal exposure. © 2009 Elsevier Ireland Ltd. All rights reserved.

Published
2010
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8. Short-term hepatic effects of depleted uranium on xenobiotic and bile acid metabolizing cytochrome P450 enzymes in the rat

Author

N. Dudoignon, Stéphane Grison, Jocelyne Aigueperse, C. Baudelin, Philippe Voisin, Patrick Gourmelon, Maâmar Souidi, C. Marquette, Isabelle Dublineau, Yann Gueguen, Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire Epigenetique et Cancer, 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 de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Section Autonome de Radiobiologie Appliquée à la Médecine (IRSN/DPHD/SARAM), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), and Département de Protection et de santé de l'Homme et de Dosimétrie, Section Autonome de Radiobiologie Appliquée à la Médecine

Subjects
Male, MESH: Microsomes, Liver, CYP3A, Health, Toxicology and Mutagenesis, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Receptors, Cytoplasmic and Nuclear, Mitochondria, Liver, MESH: Aryl Hydrocarbon Hydroxylases, MESH: Rats, Sprague-Dawley, Toxicology, Rats, Sprague-Dawley, MESH: Hydroxycholesterols, 0302 clinical medicine, MESH: Cholesterol, Cytochrome P-450 Enzyme System, MESH: Reverse Transcriptase Polymerase Chain Reaction, CYP27A1, Cytochrome P-450 CYP3A, MESH: Animals, 0303 health sciences, Bile acid, biology, Reverse Transcriptase Polymerase Chain Reaction, MESH: Gene Expression Regulation, Enzymologic, General Medicine, Isoenzymes, Cholesterol, Liver, 030220 oncology & carcinogenesis, MESH: Cytochrome P-450 Enzyme System, Microsomes, Liver, MESH: Isoenzymes, Uranium, Aryl Hydrocarbon Hydroxylases, MESH: Membrane Proteins, MESH: Mitochondria, Liver, MESH: Xenobiotics, MESH: DNA Primers, medicine.medical_specialty, MESH: Rats, medicine.drug_class, MESH: Bile Acids and Salts, MESH: Receptors, Cytoplasmic and Nuclear, Cholesterol 7 alpha-hydroxylase, Gene Expression Regulation, Enzymologic, Xenobiotics, Bile Acids and Salts, 03 medical and health sciences, Internal medicine, medicine, Animals, RNA, Messenger, Liver X receptor, 030304 developmental biology, DNA Primers, MESH: RNA, Messenger, Cytochrome P450, Membrane Proteins, Lipid metabolism, Hydroxycholesterols, MESH: Male, Rats, Endocrinology, biology.protein, MESH: Uranium, Drug metabolism, MESH: Liver
Abstract

International audience; The toxicity of uranium has been demonstrated in different organs, including the kidneys, skeleton, central nervous system, and liver. However, few works have investigated the biological effects of uranium contamination on important metabolic function in the liver. In vivo studies were conducted to evaluate its effects on cytochrome P450 (CYP) enzymes involved in the metabolism of cholesterol and xenobiotics in the rat liver. The effects of depleted uranium (DU) contamination on Sprague-Dawley were measured at 1 and 3 days after exposure. Biochemical indicators characterizing liver and kidney functions were measured in the plasma. The DU affected bile acid CYP activity: 7alpha-hydroxycholesterol plasma level decreased by 52% at day 3 whereas microsomal CYP7A1 activity in the liver did not change significantly and mitochondrial CYP27A1 activity quintupled at day 1. Gene expression of the nuclear receptors related to lipid metabolism (FXR and LXR) also changed, while PPARalpha mRNA levels did not. The increased mRNA levels of the xenobiotic-metabolizing CYP3A enzyme at day 3 may be caused by feedback up-regulation due to the decreased CYP3A activity at day 1. CAR mRNA levels, which tripled on day 1, may be involved in this up-regulation, while mRNA levels of PXR did not change. These results indicate that high levels of depleted uranium, acting through modulation of the CYP enzymes and some of their nuclear receptors, affect the hepatic metabolism of bile acids and xenobiotics.

Published
2006
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9. Changes in sleep-wake cycle after chronic exposure to uranium in rats

Author

Didier Clarençon, Philippe Lestaevel, Patrick Gourmelon, François Paquet, P. Houpert, Cyrill Bussy, B. Dhieux, Laboratoire de radiotoxicologie expérimentale, Direction de la radioprotection de l'homme, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), ANTE-INSERM U836, équipe 8, Stress et interactions neurodigestives, Unité de neuroradiobiologie, Centre de Recherche du Service de Santé des Armées-Centre de Recherche du Service de Santé des Armées, Direction de la radioprotection de l'homme, Ministère de la Défense, Sinniger, Valérie, Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX), and Direction de la radioprotection de l'homme (IRSN/DRPH)

Subjects
Male, MESH: Rats, MESH: Sleep, Central nervous system, Rapid eye movement sleep, Physiology, chemistry.chemical_element, Sleep, REM, MESH: Rats, Sprague-Dawley, Toxicology, Kidney, Rats, Sprague-Dawley, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Depleted uranium, MESH: Electroencephalography, medicine, Animals, MESH: Animals, Circadian rhythm, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Brain Chemistry, 030304 developmental biology, Brain Chemistry, 0303 health sciences, Electroencephalography, MESH: Kidney, Uranium, Sleep in non-human animals, Uranium Compounds, MESH: Sleep, REM, 6. Clean water, MESH: Male, Rats, Electrophysiology, medicine.anatomical_structure, chemistry, Toxicity, MESH: Uranium Compounds, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Sleep, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; Uranium is a heavy metal known to induce toxicity in kidneys. It is also known to enter the central nervous system, thus inducing neurophysiological effects, after exposure to relatively high concentrations. The effect of chronic uranium exposure (40 mg l(-1) in drinking water, for 90 days) on electroencephalographic architecture has been studied on freely moving rats using a telemetry technique. The main effects of uranium on the sleep-wake cycle were an increase in rapid eye movement sleep (REM-sleep) and theta band power during the light period, as early as Day 30 after exposure commenced. The most probable explanation for these effects is that uranium directly affects the brain. This increase in REM-sleep was previously described in human depression or models of chronically stressed rats and it may be assimilated with some protective or compensatory mechanisms.

Published
2005
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