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Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase
T Tsuzuki1, A Egashira, H Igarashi
1Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. tsuzuki@med.kyushu-u.ac.jp
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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