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

Abstract

The aminothiols cysteamine (CSM) and 2-[(aminopropyl)amino] ethanethiol (WR-1065) are radioprotectors, in that they reduce the mutagenic and potentially lethal consequences of ionizing radiation. We have studied the effects of these compounds on the induction of gene conversion at the trp5 locus in Saccharomyces cerevisiae strain D7 by two chemical mutagens: bleomycin (BLM) and β-propiolactone ( β-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 β-PL by about 95%. The maximum reduction in the recombinagenic activity of BLM was 91% with CSM and 89% with WR-1065. Although the antimutagenic effects of the aminothiols against β-PL and BLM appear to be similar, they stem from different underlying mechanisms. Aminothiols protect against the recombinagenicity of β-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.