title: Mutagenesis and anti-mutagenesis in Salmonella: influence of ethionine and caffeine on yields of mutations induced by 2-aminopurine and 9-aminoacridine.
abstract: Ethionine, the ethyl analogue of methionine, slightly reduced the yield of reversions of the hisC3076 frameshift marker induced by 9-aminoacridine (9AA) in an excision-proficient strain of Salmonella typhimurium, but completely abolished mutagenesis by 9AA in the excision-deficient uvrB-deletion strain TA1537. No toxic effects of ethionine were apparent in either the excision-proficient or the excision-deficient strain. Because of the differential effects of ethionine on mutagenesis in the two strains, it seemed possible that an ethionine-sensitive step in the process(es) leading to fixation of 9AA-induced mutations might be compensated for by the uvrA,B,C+ excision-repair system. To further test this possibility, we used caffeine (a compound known to significantly reduce the efficacy of the excision-repair process) as a co-treatment with ethionine for cells of an excision-proficient strain exposed to 9AA. Treatment with caffeine alone or ethionine alone had very little effect on reversion yield, whereas co-treatment with the two agents abolished 9AA mutagenesis. It appeared, therefore, that either the caffeine-sensitive pathway or the ethionine-sensitive pathway needed to be functioning if 9AA-induced reversions of hisC3076 marker were to be detected. Addition of methionine to cells of the excision-deficient strain exposed to 9AA restored their ability to be mutated by 9AA, however. In a base-pair substitution back-mutation system, ethionine slightly enhanced the yields of revertants of the trpE8 marker induced by 2-aminopurine (2AP) in both an excision-proficient strain (at all 2AP dose levels tested) and an excision-deficient strain (only at the lower dose levels). In the excision-deficient strain, doses of 2AP above 300 micrograms/plate were highly toxic when ethionine was also present. It was for this reason that no 2AP-induced revertants were recovered at the higher 2AP concentrations. Treatment of the trpE8 strain with methionine also enhanced the yield of 2AP-induced revertants of this marker.
mesh_terms: D015075:2-Aminopurine / Q000633:toxicity*; D000225:Adenine / Q000031:analogs & derivatives*; D000585:Aminacrine / Q000633:toxicity*; D000609:Aminoacridines / Q000633:toxicity*; D002110:Caffeine / Q000494:pharmacology*; D005001:Ethionine / Q000494:pharmacology*; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects; D013045:Species Specificity
chemical_list: D000609:Aminoacridines; D009153:Mutagens; D002110:Caffeine; D015075:2-Aminopurine; D000585:Aminacrine; D000225:Adenine; D005001:Ethionine