DNA damage and oxidative stress induced by CeO2 nanoparticles in human dermal fibroblasts: Evidence of a clastogenic effect as a mechanism of genotoxicity

International audienceThe broad range of applications of cerium oxide (CeO2) nanoparticles (nano-CeO2) has attractedindustrial interest, resulting in greater exposures to humans and environmental systems in thecoming years. Their health effects and potential biological impacts need to be determined forrisk assessment. The aims of this study were to gain insights into the molecular mechanismsunderlying the genotoxic effects of nano-CeO2 in relation with their physicochemicalproperties. Primary human dermal fibroblasts were exposed to environmentally relevantdoses of nano-CeO2 (mean diameter, 7 nm; dose range, 6 x10-5–6x10-3 g/l corresponding toa concentration range of 0.22–22 mM) and DNA damages at the chromosome level wereevaluated 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 ofcentromere protein A in micronuclei were used to distinguish between induction of structuralor numerical chromosome changes (i.e. clastogenicity or aneuploidy). The results provide thefirst evidence of a genotoxic effect of nano-CeO2, (while not significant with micro-CeO2) by aclastogenic mechanism. The implication of oxidative mechanisms in this genotoxic effect wasinvestigated by (i) assessing the impact of catalase, a hydrogen peroxide inhibitor, and (ii) bymeasuring lipid peroxidation and glutathione status and their reversal by application ofN-acetylcysteine, a precusor of glutathione synthesis in cells. The data are consistent with theimplication of free radical-related mechanisms in the nano-CeO2-induced clastogenic effect,that can be modulated by inhibition of cellular hydrogen peroxide release