Two mechanisms of antimutagenicity of the aminothiols cysteamine and WR-1065 in Saccharomyces cerevisiae

The aminothiols cysteamine (CSM) and 2-[(aminopropyl)amino] ethanethiol (WR -1065) are radioprotectors, in that they reduce the mutagenic and potential ly lethal consequences of ionizing radiation. We have studied the effects o f these compounds on the induction of gene conversion at the trp5 locus in Saccharomyces cerevisiae strain D7 by two chemical mutagens: bleomycin (BLM ) and beta-propiolactone (beta-PL). Both mutagens are potent recombinagens in this assay, giving rise to trp5 convertant frequencies greater than 10(- 3) CSM and WR-1065 are effective antimutagens, reducing the recombinagenic effect of beta-PL by about 95%. The maximum reduction in the recombinagenic activity of BLM was 91% with CSM and 89% with WR-1065. Although the antimu tagenic effects of the aminothiols against beta-PL and BLM appear to be sim ilar, they stem from different underlying mechanisms. Aminothiols protect a gainst the recombinagenicity of beta-PL through direct inactivation of the electrophilic mutagen by the nucleophilic antimutagen. They protect against that of BLM through modification of physiological conditions, most notably by depletion of oxygen required for BLM activity. (C) 1999 Elsevier Scienc e Ltd. All rights reserved.