Open AccessSpontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase
Author(s) -
Teruhisa Tsuzuki,
Akinori Egashira,
Hisato Igarashi,
Tomoo Iwakuma,
Yoko Nakatsuru,
Yoshihiro Tominaga,
Hisaya Kawate,
Kazuki Nakao,
Kenji Nakamura,
Fumio Ide,
Shinobu Kura,
Yusaku Nakabeppu,
Motoya Katsuki,
Takatoshi Ishikawa,
Mutsuo Sekiguchi
Publication year - 2001
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.191086798
Subject(s) - carcinogenesis , transversion , gene , mutagenesis , biology , microbiology and biotechnology , mutation , oxidative stress , genetics , biochemistry
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.