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Mutagenesis, Vol. 14, No. 2, 233-238, March 1999
© 1999 UK Environmental Mutagen Society/Oxford University Press

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

Paola Poli1, Annamaria Buschini, Alessia Candi and Carlo Rossi

Istituto di Genetica, Università degli Studi di Parma, viale delle Scienze, 43100 Parma, Italy

The genotoxic effects of the antiblastic drug bleomycin were studied in the D7 strain of Saccharomyces cerevisiae and on its derivative mitochondrial mutant {rho}° 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.

1 To whom correspondence should be addressed. Tel: +39 0521 905608; Fax: + 39 0521 905604; Email: mutgen{at}ipruniv.cce.unipr.it


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