Genotoxicity of tungsten carbide–cobalt (WC–Co) nanoparticles in vitro: Mechanisms-of-action studies

Publication date: February 2015 Source:Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Volume 779 Author(s): Hélène Moche , Dany Chevalier , Hervé Vezin , Nancy Claude , Elisabeth Lorge , Fabrice Nesslany 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.
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research