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Tsuzuki, T. et al.

Tsuzuki, Egashira, Igarashi, Iwakuma, Nakatsuru, Tominaga, Kawate, Nakao, Nakamura, Ide, Kura, Nakabeppu, Katsuki, Ishikawa, Sekiguchi,

Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase.

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.[1]

References

Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase. 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. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]

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