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

The exposure of mammalian cells or tumors for weeks or months to low non-lethal doses of cytostatic drugs may induce multi-drug resistance, which can be enhanced by a variety of DNA-damaging agents. In yeast multi-drug resistance to a 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.