Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2148782 | Mutation Research/Genetic Toxicology and Environmental Mutagenesis | 2009 | 8 Pages |
Abstract
The trace element selenium (Se), once known only for its potential toxicity, is now a well-established essential micronutrient for mammals. The organoselenium compound diphenyl diselenide (DPDS) has shown interesting antioxidant and neuroprotective activities. On the other hand, this compound has also presented pro-oxidant and mutagenic effects. The compound 3â²3-ditrifluoromethyldiphenyl diselenide (DFDD), a structural analog of diphenyl diselenide, has proven antipsychotic activity in mice. Nevertheless, as opposed to DPDS, little is known on the biological and toxicological properties of DFDD. In the present study, we report the genotoxic effects of the organoselenium compound DFDD on Salmonella typhimurium, Saccharomyces cerevisiae and Chinese hamster lung fibroblasts (V79 cells). DFDD protective effects against hydrogen peroxide (H2O2)-induced DNA damage in vitro are demonstrated. DFDD did not cause mutagenic effects on S. typhimurium or S. cerevisiae strains; however, it induced DNA damage in V79 cells at doses higher than 25 μM, as detected by comet assay. DFDD protected S. typhimurium and S. cerevisiae against H2O2-induced mutagenicity, and, at doses lower than 12.5 μM, prevented H2O2-induced genotoxicity in V79 cells. The in vitro assays demonstrated that DFDD mimics catalase activity better than DPDS, but neither presents superoxide dismutase action. The products of the reactions of DFDD or DPDS with H2O2 were different, as determined by electrospray mass spectrometry analysis (ESI-MS). These results suggest that DFDD is not mutagenic for bacteria or yeast; however, it may induce weak genotoxic effects on mammalian cells. In addition, DFDD has a protective effect against H2O2-induced damage probably by mimicking catalase activity, and the distinct products of the reaction DFDD with H2O2 probably have a fundamental role in the protective effects of DFDD.
Keywords
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Authors
Miriana da Silva Machado, Izabel Vianna Villela, Dinara Jaqueline Moura, Renato Moreira Rosa, Mirian Salvador, Norberto P. Lopes, Antonio Luiz Braga, Rafael Roesler, Jenifer Saffi, João Antonio P. Henriques,