title: Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase.
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.
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. tsuzuki@med.kyushu-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: A
authors.initials: A
authors.lastname: Egashira
authors.forename: H
authors.initials: H
authors.lastname: Igarashi
authors.forename: T
authors.initials: T
authors.lastname: Iwakuma
authors.forename: Y
authors.initials: Y
authors.lastname: Nakatsuru
authors.forename: Y
authors.initials: Y
authors.lastname: Tominaga
authors.forename: H
authors.initials: H
authors.lastname: Kawate
authors.forename: K
authors.initials: K
authors.lastname: Nakao
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: F
authors.initials: F
authors.lastname: Ide
authors.forename: S
authors.initials: S
authors.lastname: Kura
authors.forename: Y
authors.initials: Y
authors.lastname: Nakabeppu
authors.forename: M
authors.initials: M
authors.lastname: Katsuki
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
authors.forename: M
authors.initials: M
authors.lastname: Sekiguchi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000483:Alleles; D000818:Animals; D001755:Blastocyst; D015153:Blotting, Western; D002678:Chimera; D002999:Clone Cells; D003433:Crosses, Genetic; D004249:DNA Damage; D017931:DNA Primers; D045643:DNA Repair Enzymes; D005091:Exons; D005260:Female; D008099:Liver / Q000201:enzymology; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011995:Recombination, Genetic; D015183:Restriction Mapping; D013274:Stomach Neoplasms / Q000235:genetics
chemical_list: D017931:DNA Primers; D010744:Phosphoric Monoester Hydrolases; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes