title: Genotoxicity of tungsten carbide-cobalt (WC-Co) nanoparticles in vitro: mechanisms-of-action studies.
abstract: 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.
authors: Institut Pasteur de Lille, 59019 Lille Cedex, France; Servier Group, 45520 Gidy, France; EA 4483, Université Lille 2, 59000 Lille, France.
authors: Hélène
authors: H
authors: Moche
authors: EA 4483, Université Lille 2, 59000 Lille, France.
authors: Dany
authors: D
authors: Chevalier
authors: LASIR, Université Lille 1, France.
authors: Hervé
authors: H
authors: Vezin
authors: Servier Group, 45520 Gidy, France.
authors: Nancy
authors: N
authors: Claude
authors: Servier Group, 45520 Gidy, France.
authors: Elisabeth
authors: E
authors: Lorge
authors: Institut Pasteur de Lille, 59019 Lille Cedex, France; EA 4483, Université Lille 2, 59000 Lille, France. Electronic address: fabrice.nesslany@pasteur-lille.fr.
authors: Fabrice
authors: F
authors: Nesslany
mesh_terms: D024422:Aneugens / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000187:drug effects; D003035:Cobalt / Q000737:chemistry / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017973:Tungsten Compounds / Q000737:chemistry / Q000633:toxicity*
chemical_list: D024422:Aneugens; D009153:Mutagens; D017382:Reactive Oxygen Species; D017973:Tungsten Compounds; C002802:tungsten carbide; D003035:Cobalt
keywords: Aneugenic effect; Clastogenic effect; Nanomaterials; Oxidative DNA damage; Reactive oxygen species