DNA damage and oxidative stress induced by CeO2 nanoparticles in human dermal fibroblasts: Evidence of a clastogenic effect as a mechanism of genotoxicity
| Autor: | Virginie Tassistro, Mélanie Auffan, Jérôme Rose, Sylvia Pietri, Laila Benameur, Wei Liu, Mathieu Cassien, Jean-Yves Bottero, Pierre Stocker, Marcel Culcasi, Hidayat Rahmouni, Alain Botta |
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| Přispěvatelé: | Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Collège de France (CdF)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université (AMU)-Avignon Université (AU), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Surface Properties
DNA damage [SDV]Life Sciences [q-bio] Primary Cell Culture Biomedical Engineering free radicals Biology Toxicology medicine.disease_cause Lipid peroxidation chemistry.chemical_compound glutathione status medicine Humans [CHIM]Chemical Sciences Colloids Particle Size Hydrogen peroxide Cells Cultured Skin Genetics Cerium Glutathione Fibroblasts nanoceria Oxidative Stress chemistry Catalase Micronucleus test Biophysics biology.protein Nanoparticles nanogenotoxicity Cytokinesis-blocked micronucleus assay Genotoxicity Oxidative stress DNA Damage Mutagens |
| Zdroj: | Nanotoxicology Nanotoxicology, Taylor & Francis, 2015, 9 (6), pp. 696-705. ⟨10.3109/17435390.2014.968889⟩ Nanotoxicology, Vol. 9, No 6 (2015) pp. 696-705 Nanotoxicology, 2015, 9 (6), pp. 696-705. ⟨10.3109/17435390.2014.968889⟩ |
| ISSN: | 1743-5390 1743-5404 |
| DOI: | 10.3109/17435390.2014.968889⟩ |
| Popis: | The broad range of applications of cerium oxide (CeO2) nanoparticles (nano-CeO2) has attracted industrial interest, resulting in greater exposures to humans and environmental systems in the coming years. Their health effects and potential biological impacts need to be determined for risk assessment. The aims of this study were to gain insights into the molecular mechanisms underlying the genotoxic effects of nano-CeO2 in relation with their physicochemical properties. Primary human dermal fibroblasts were exposed to environmentally relevant doses of nano-CeO2 (mean diameter, 7 nm; dose range, 6 x10-5–6x10-3 g/l corresponding to a concentration range of 0.22–22 mM) and DNA damages at the chromosome level were evaluated by genetic toxicology tests and compared to that induced in cells exposed to micro- CeO2 particles (mean diameter, 320 nm) under the same conditions. For this purpose, cytokinesis-blocked micronucleus assay in association with immunofluorescence staining of centromere protein A in micronuclei were used to distinguish between induction of structural or numerical chromosome changes (i.e. clastogenicity or aneuploidy). The results provide the first evidence of a genotoxic effect of nano-CeO2, (while not significant with micro-CeO2) by a clastogenic mechanism. The implication of oxidative mechanisms in this genotoxic effect was investigated by (i) assessing the impact of catalase, a hydrogen peroxide inhibitor, and (ii) by measuring lipid peroxidation and glutathione status and their reversal by application of N-acetylcysteine, a precusor of glutathione synthesis in cells. The data are consistent with the implication of free radical-related mechanisms in the nano-CeO2-induced clastogenic effect, that can be modulated by inhibition of cellular hydrogen peroxide release. |
| Databáze: | OpenAIRE |
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