Ascorbic Acid and Thiol Antioxidants Suppress Spontaneous Mutagenesis in a Cu,Zn-Superoxide Dismutase-Deficient Mutant of Saccharomyces cerevisiae.

K. Nagira, S. Tamura, S. Kawano, S. Ikeda

Cu,Zn-superoxide dismutase (SOD1) is a critical enzyme in the cellular antioxidant system.  The yeast Saccharomyces cerevisiae SOD1 mutant (SOD1∆) exhibits a moderate mutator phenotype under aerobic conditions.  The mutation frequency of a SOD1∆ strain determined by a CAN1 forward-mutation assay was about 12-fold higher than that of the parental strain.  Base substitutions G·C → T·A, G·C → A·T, and A·T → C·G were most commonly observed in CAN1 mutants, indicating that the mutations are caused mainly by oxidative DNA damage.  The mutation frequency of SOD1∆ was reduced in a dose-dependent manner by cultivating it in the presence of ascorbic acid, implying that the SOD1∆ mutant can be used as a tester strain for small molecule antioxidants.  Exogenous glutathione and N-acetylcystein also alleviated the mutator phenotype.  The results indicate that ascorbic acid and thiol antioxidants are able to efficiently protect cells against oxidative damage-induced mutagenesis.  In this assay, no apparent mutation suppression was seen for other categories of antioxidants including resveratrol, Trolox and melatonin.

Genes and Environment

日本環境変異原学会

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