The effects of antioxidants and enzymes involved in glutathione metabolism on mutagenesis by glutathione and L-cysteine.

The effects of small molecular weight antioxidants and antioxidant enzymes on the mutagenicities of glutathione (GSH) and L-cysteine were studied in Salmonella typhimurium strain TA102. GSH and cysteine mutagenesis were inhibited by antioxidants and radical scavengers such as alpha-tocopherol, Trolox C, butylated hydroxyanisole (BHA), and retinyl acetate. Superoxide dismutase (SOD) had no effect, but catalase and horseradish peroxidase (HRP) inhibited mutagenesis. The heat-denatured enzymes had no effect on mutagenesis. Cysteine mutagenesis was enhanced by native and by heat-denatured rat-kidney post-mitochondrial supernatant, and by ferric ions. H2O2 and the H2O2-generating system of glucose-glucose oxidase (GOX) were mutagenic in TA102. Synergistic increases in mutagenesis were obtained in systems containing combinations of GSH or cysteine, with either H2O2 or the H2O2-generating system of glucose-GOX. GSH peroxidase (GPX) had no effect on mutagenesis of GSH or of H2O2, whereas the synergistic increase in mutagenesis by a combination of GSH and H2O2 was effectively inhibited by GPX. The results suggest strongly that, at least in biochemically-defined systems, GSH and cysteine mutagenesis are oxidative in nature, and involve reactive forms of oxygen and/or other radicals.