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.
Stark
A A
AA
Department of Biochemistry, Tel-Aviv University, Israel.
Pagano
D A
DA
Glass
G
G
Kamin-Belsky
N
N
Zeiger
E
E
D000818:Animals; D016587:Antimutagenic Agents / Q000378:metabolism / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001711:Biotransformation; D002374:Catalase / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism / Q000633:toxicity*; D004347:Drug Interactions; D005609:Free Radicals; D005949:Glucose Oxidase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D007502:Iron Chelating Agents / Q000633:toxicity; D007668:Kidney / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000633:toxicity; D013482:Superoxide Dismutase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D016587:Antimutagenic Agents; D000975:Antioxidants; D005609:Free Radicals; D007502:Iron Chelating Agents; D009153:Mutagens; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D005949:Glucose Oxidase; D006735:Horseradish Peroxidase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D003545:Cysteine