Bleomycin genotoxicity alteration by glutathione and cytochrome P-450 cellular content in respiratory proficient and deficient strains of Saccharomyces cerevisiae

The genotoxic effects of the antiblastic drug bleomycin were studied in the D7 strain of Saccharomyces cerevisiae and on its derivative mitochondrial mutant rho degrees at different cellular concentrations of two drug metabol izing systems, glutathione (GSH) and cytochrome P-450. Bleomycin mutagenic activity was evaluated as frequencies of mitotic gene conversion, reversion and total aberrations under different physiological conditions. In the D7 strain, petite mutant induction was also detected. This is important due to the role of the mitochondrial genome in cancer induction, ageing and degen erative diseases. Both strains showed higher convertant than revertant indu ction. At high cytochrome P-450 levels, bleomycin-induced gene conversion w as enhanced in both strains although mitochondrial functionality showed a d etoxicant role while cellular GSH content decreased the induction of conver tants only in the respiratory proficient strain. Cell metabolic conditions, such as cell cycle, aerobic/hypoxic conditions of the cell and content of drug metabolizing enzymes, appeared to interact with the genotoxic effectiv eness of bleomycin, Moreover, the usefulness of S. cerevisiae as a model or ganism for drug assessment for mutagenicity was emphasized.