191 Mutagenesis induced by X-irradiation in Mth1 knockout mice

Oxidized forms of nucleotides within DNA or precursor pools were generated by oxygen radicals, and are thought to play an important role in mutagenesis as well as carcinogenesis. In particular, 8-oxo-dGTP is a highly mutagenic substrate for DNA synthesis. Mammalian MTH1 hydrolyzes 8-oxo-dGTP to mono...

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Published inJOURNAL OF RADIATION RESEARCH Vol. 44; no. 4; p. 433
Main Authors Shinobu KURA, Katsumi SAKAMOTO, Yoshimichi NAKATSU, Yusaku NAKABEPPU, Mutsuo SEKIGUCHI, Teruhisa TSUZUKI
Format Journal Article
LanguageJapanese
Published THE JAPAN RADIATION RESEARCH SOCIETY 2003
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Summary:Oxidized forms of nucleotides within DNA or precursor pools were generated by oxygen radicals, and are thought to play an important role in mutagenesis as well as carcinogenesis. In particular, 8-oxo-dGTP is a highly mutagenic substrate for DNA synthesis. Mammalian MTH1 hydrolyzes 8-oxo-dGTP to monophosphate, thereby preventing occurrence of mutations caused by oxygen radicals. Since ionizing radiation induces oxygen radicals in mammalian cells, Mth1 deficient mice might show a hypermutability in response to ionizing radiation. In the present study, we examine this possibility by analyzing X-ray induced mutagenesis in Mth1 deficient mice carrying E. coli rpsL transgene as a reporter. When analysed DNA samples recovered from spleens of Mth1 deficient and of wild-type mice, we found a slight increase in mutation frequency in spleens of Mth1 deficient mice as compared with findings in wild-type mice after exposure to 4 Gy of X-rays. Mutation spectrum analysis revealed an increase in the frequency of A：T to G：C transition in Mth1 deficient mice irradiated by X-ray.
ISSN:0449-3060