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.
Fahrig
R
R
Abteilung Genetik, Fraunhofer-Institut für Toxikologie und Aerosolforschung, Hannover, F.R.G.
Kaspers
I
I
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000222:Adaptation, Physiological; D016009:Chi-Square Distribution; D003433:Crosses, Genetic; D004352:Drug Resistance, Microbial / Q000235:genetics; D005799:Genes, Dominant; D005800:Genes, Fungal; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D011995:Recombination, Genetic / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D013172:Spores, Fungal / Q000235:genetics; D014265:Triethylenemelamine / Q000494:pharmacology
D009153:Mutagens; D015112:4-Nitroquinoline-1-oxide; D014265:Triethylenemelamine