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Genotoxicity of tungsten carbide–cobalt (WC–Co) nanoparticles in vitro: Mechanisms-of-action studies
Ist Teil von
Mutation research. Genetic toxicology and environmental mutagenesis, 2015-02, Vol.779, p.15-22
Ort / Verlag
Netherlands: Elsevier B.V
Erscheinungsjahr
2015
Quelle
MEDLINE
Beschreibungen/Notizen
•WC–Co NP induce structural and numerical chromosome aberrations.•FISH analysis of micronuclei shows the induction of clastogenic and aneugenic events.•WC–Co NP induce FPG-sensitive sites depending on the cell type in the comet assay.•WC–Co NP generate OH radicals in suspensions with and without cells.•OH radicals are produced intrinsically and through Fenton-like reactions.
We showed previously that tungsten carbide–cobalt (WC–Co) nanoparticles (NP) can be used as a nanoparticulate positive control in some in vitro mammalian genotoxicity assays. Here, we investigate the mechanisms of action involved in WC–Co NP genotoxicity in L5178Y mouse lymphoma cells and primary human lymphocytes, in vitro. Data from the micronucleus assay coupled with centromere staining and from the chromosome-aberration assay show the involvement of both clastogenic and aneugenic events. Experiments with the formamidopyrimidine DNA glycosylase (FPG)-modified comet assay showed a slight (non-significant) increase in FPG-sensitive sites in the L5178Y mouse lymphoma cells but not in the human lymphocytes. Electron paramagnetic resonance spin-trapping results showed the presence of hydroxyl radicals (OH) in WC–Co NP suspensions, with or without cells, but with time-dependent production in the presence of cells. However, a significant difference in OH production was observed between human lymphocytes from two different donors. Using H2O2, we showed that WC–Co NP can participate in Fenton-like reactions. Thus, OH might be produced either via intrinsic generation by WC–Co NP or through a Fenton-like reaction in the presence of cells.