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 degree at different cellular concentrations of two drug metabolizing 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 degenerative diseases. Both strains showed higher convertant than revertant induction. At high cytochrome P-450 levels, bleomycin-induced gene conversion was enhanced in both strains although mitochondrial functionality showed a detoxicant role while cellular GSH content decreased the induction of convertants 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 effectiveness of bleomycin. Moreover, the usefulness of S.cerevisiae as a model organism for drug assessment for mutagenicity was emphasized.
Poli
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Istituto di Genetica, Università degli Studi di Parma, Italy. mutgen@ipruniv.cce.unipr.it
Buschini
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Candi
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Rossi
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D001761:Bleomycin / Q000633:toxicity*; D018929:Cell Culture Techniques; D002869:Chromosome Aberrations; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism*; D016296:Mutagenesis; D009152:Mutagenicity Tests / Q000379:methods; D010101:Oxygen Consumption / Q000187:drug effects*; D017354:Point Mutation; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000187:drug effects*
D004272:DNA, Mitochondrial; D001761:Bleomycin; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione