Literature DB >> 11572992

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

T Tsuzuki1, A Egashira, H Igarashi, T Iwakuma, Y Nakatsuru, Y Tominaga, H Kawate, K Nakao, K Nakamura, F Ide, S Kura, Y Nakabeppu, M Katsuki, T Ishikawa, M Sekiguchi.   

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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Year:  2001        PMID: 11572992      PMCID: PMC58751          DOI: 10.1073/pnas.191086798

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  44 in total

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Authors:  M Kobayashi; Y Ohara-Nemoto; M Kaneko; H Hayakawa; M Sekiguchi; K Yamamoto
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