Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase |
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Authors: | Tsuzuki T Egashira A Igarashi H Iwakuma T Nakatsuru Y Tominaga Y Kawate H Nakao K Nakamura K Ide F Kura S Nakabeppu Y Katsuki M Ishikawa T Sekiguchi M |
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Affiliation: | Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. tsuzuki@med.kyushu-u.ac.jp |
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Abstract: | Oxygen radicals, which can be produced through normal cellular metabolism, are thought to play an important role in mutagenesis and tumorigenesis. Among various classes of oxidative DNA damage, 8-oxo-7,8-dihydroguanine (8-oxoG) is most important because of its abundance and mutagenicity. The MTH1 gene encodes an enzyme that hydrolyzes 8-oxo-dGTP to monophosphate in the nucleotide pool, thereby preventing occurrence of transversion mutations. By means of gene targeting, we have established MTH1 gene-knockout cell lines and mice. When examined 18 months after birth, a greater number of tumors were formed in the lungs, livers, and stomachs of MTH1-deficient mice, as compared with wild-type mice. The MTH1-deficient mouse will provide a useful model for investigating the role of the MTH1 protein in normal conditions and under oxidative stress. |
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