Genotoxic activity of five haloacetonitriles: comparative investigations in the single cell gel electrophoresis (comet) assay and the ames-fluctuation test.
Halogenated acetonitriles (HANs) are known to be water disinfectant by-products. Their mutagenicity and carcinogenicity have been shown in different test systems in vivo and in vitro. They also have clastogenic properties. In this study, the ability of HAN to induce single-strand breaks on the DNA of HeLa S3 cells was investigated using the single-cell gel electrophoresis (SCGE) assay, which could be a good tool with which to evaluate the genotoxicity of chlorinated water. The results were compared to those obtained in the Ames fluctuation test using the Salmonella typhimurium TA 100 strain without activation. With the Ames fluctuation test, a mutagenic effect was observed for chloroacetonitrile (MCAN), dichloroacetonitrile (DCAN), and trichloroacetonitrile (TCAN). No mutagenic effect was found with bromoacetonitrile (MBAN) or dibromoacetonitrile (DBAN). In the SCGE assay, all five HANs induced DNA damage in HeLa S3 cells, increasing the mean tail moment significantly. For each compound, a dose-effect relation was observed. This study shows that the SCGE assay has greater sensitivity for assessing the genotoxicity of HAN than does the Ames-fluctuation test. Brominated acetonitriles were more genotoxic than chlorinated acetonitriles in the SCGE assay, and the genotoxicity increased with the number of halogenated atoms of the compound. This behavior had already been found with other genotoxicity tests.
INSERM U420, Département Environnement et Santé Publique, Faculté de Médecine, Vandoeuvre-lès-Nancy, France.
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Muller-Pillet
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Joyeux
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Ambroise
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P
Hartemann
D000097:Acetonitriles / Q000633:toxicity*; D020552:Comet Assay; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014874:Water Pollutants, Chemical / Q000633:toxicity
D000097:Acetonitriles; D014874:Water Pollutants, Chemical; C029549:trichloroacetonitrile; C069277:chloroacetonitrile; C051716:dichloroacetonitrile; C051715:dibromoacetonitrile