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

被引：253

作者：

Tsuzuki, T ^{[1
]}

Egashira, A

Igarashi, H

Iwakuma, T

Nakatsura, Y

Tominaga, Y

Kawate, H

Nakao, K

Nakamura, K

Ide, F

Kura, S

Nakabeppu, Y

Katsuki, M

Ishikawa, T

Sekiguchi, M

机构：

[1] Kyushu Univ, Med Inst Bioregulat, Fukuoka 8128582, Japan

[2] Kyushu Univ, Grad Sch, Fac Med Sci, Dept Med Biophys & Radiat Biol, Fukuoka 8128582, Japan

[3] Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo 1130033, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2001年 / 98卷 / 20期

关键词：

D O I：

10.1073/pnas.191086798

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：11456 / 11461

页数：6

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