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, 554 (1-2), 365-74

Suppression of Chemically Induced and Spontaneously Occurring Oxidative Mutagenesis by Three Alleles of Human OGG1 Gene Encoding 8-hydroxyguanine DNA Glycosylase

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Suppression of Chemically Induced and Spontaneously Occurring Oxidative Mutagenesis by Three Alleles of Human OGG1 Gene Encoding 8-hydroxyguanine DNA Glycosylase

Su-Ryang Kim et al. Mutat Res.

Abstract

8-Hydroxyguanine (8-OH-G) is an oxidatively damaged guanine base that causes G:C to T:A transversion mutations. To counteract the mutagenicity of 8-OH-G in DNA, humans possess the hOGG1 gene, which encodes 8-OH-G DNA glycosylase. Interestingly, genetic polymorphisms at codon 326 (hOGG1-Ser326 versus hOGG1-Cys326) and at codon 46 (hOGG1-Arg46 versus hOGG1-Gln46) exist in human populations. hOGG1-Ser326 and -Cys326 have Arg at codon 46, and hOGG1-Gln46 has Ser at codon 326. In this study, we examined the abilities of three forms of GST-hOGG1 (hOGG1-Ser326, -Cys326 and -Gln46) to suppress chemically induced oxidative mutagenesis using Salmonella typhimurium strains YG3001 and YG3002. These strains are the mutMST derivatives of Ames tester strains TA1535 (uvrB-) and TA1975 (uvrB+), respectively. The mutMST gene encodes a functional counterpart of the OGG1 gene. Mutations induced by 4-nitroquinoline 1-oxide were by more than 95% suppressed by the expression of any of three forms of GST-hOGG1 in strain YG3002. Expression of GST-hOGG1 also reduced by 40 and 60%, respectively, the numbers of His+ revertants induced by methylene blue plus visible light and benzo[a]pyrene plus visible light in strain YG3001. hOGG1-Gln46 displayed a slightly weaker ability to suppress the mutations induced by methylene blue plus visible light than did other two forms although the differences were not statistically significant. About 85 and 95% of spontaneous mutagenesis in strain YG3021 and YG3022, the mutMST mutYST double mutants of strain TA1535 and TA1975, respectively, were suppressed by the expression of any of hOGG1 alleles. hOGG1-Gln46 displayed a weaker suppression than did other two forms in strain YG3022 and the difference was statistically significant. These results suggest that three alleles of the hOGG1 gene efficiently suppress chemically induced and spontaneously occurring oxidative mutagenesis, and that hOGG1-Gln46 may have a weaker ability to suppress the mutations.

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