Ogg1 knockout-associated lung tumorigenesis and its suppression by Mth1 gene disruption.
Using Mth1 and Ogg1 knockout mice, we evaluated the roles of these enzymes to prevent tumorigenesis and the accumulation of 8-oxoguanine (8-oxoG) in DNA. We found that lung adenoma/carcinoma spontaneously developed in Ogg1 knockout mice approximately 1.5 years after birth in which 8-oxoG was found to accumulate in their genomes. The mean number of tumors/mouse was 0.71 for the Ogg1 knockout mice, which was five times higher than that observed in wild-type mice (0.14). Although the accumulation of 8-oxoG was also confirmed in the Ogg1, Mth1 double knockout mice, we found no tumor in the lungs of these mice. This observation suggests that Mth1 gene disruption resulted in a suppression of the tumorigenesis caused by an Ogg1 deficiency.
Sakumi
Kunihiko
K
Division of Neurofunctional Genomics, Medical Institute of Bioregulation, Kyushu University and CREST, JST, Fukuoka 812-8582, Japan. sakumi@bioreg.kyushu-u.ac.jp
Tominaga
Yohei
Y
Furuichi
Masato
M
Xu
Ping
P
Tsuzuki
Teruhisa
T
Sekiguchi
Mutsuo
M
Nakabeppu
Yusaku
Y
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D045643:DNA Repair Enzymes; D043382:DNA-Formamidopyrimidine Glycosylase; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009699:N-Glycosyl Hydrolases / Q000235:genetics*; D010375:Pedigree; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*
C024829:8-hydroxyguanine; D006147:Guanine; D010744:Phosphoric Monoester Hydrolases; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes