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Adaptive resistance of Saccharomyces cerevisiae to chronic treatment with mutagens being due to a dominant mutation

: Fahrig, R.; Kaspers, I.


Mutation research 228 (1990), No.2, pp.141-148
ISSN: 0027-5107
Journal Article
Fraunhofer ITA ( ITEM) ()
cytostatic drug; DNA; DNA-damaging agent; DNA repair; mutagen; mutagenic substance; mutation; saccharomyces cerevisiae

The exposure of mammalian cells or tumors for weeks or months to low non-lethal doses of cystostatic drugs may induce multi-drug resistance, which can be enhanced by a variety of DNA-damaging agents. In yeast multi-drug resistance to variety of drugs has been observed. DNA-damaging agents have not yet been tested. As the appearance of resistance is the result of long-term exposure, we decided to extend the application of test substances to a period of up to 400 days. In such long-term experiments S. cerevisiae MP1 adapted to treatment with low doses of mutagens. Consistent results were obtained for both alkylating and non-alkylating mutagenic substances. Furthermore, the adaptive resistance to the alkylating agent also adapted cells to the non-alkylating agent, which implies that there may be a single pathway for mutagens with different modes of action. Random spore analysis of adapted yeast cells and the back-cross to the parental wild type indicates that a single dominant mutation is responsible for the adaptive resistance.