TY - JOUR
T1 - Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase
AU - Tsuzuki, Teruhisa
AU - Egashira, Akinori
AU - Igarashi, Hisato
AU - Iwakuma, Tomoo
AU - Nakatsuru, Yoko
AU - Tominaga, Yohei
AU - Kawate, Hisaya
AU - Nakao, Kazuki
AU - Nakamura, Kenji
AU - Ide, Fumio
AU - Kura, Shinobu
AU - Nakabeppu, Yusaku
AU - Katsuki, Motoya
AU - Ishikawa, Takatoshi
AU - Sekiguchi, Mutsuo
PY - 2001/9/25
Y1 - 2001/9/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035949687&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035949687&partnerID=8YFLogxK
U2 - 10.1073/pnas.191086798
DO - 10.1073/pnas.191086798
M3 - Article
C2 - 11572992
AN - SCOPUS:0035949687
SN - 0027-8424
VL - 98
SP - 11456
EP - 11461
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 20
ER -