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Cancer Res. 2003 Mar 1;63(5):902-5.

Ogg1 knockout-associated lung tumorigenesis and its suppression by Mth1 gene disruption.

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1
Division of Neurofunctional Genomics, Medical Institute of Bioregulation, Kyushu University and CREST, JST, Fukuoka 812-8582, Japan. sakumi@bioreg.kyushu-u.ac.jp

Abstract

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.

PMID:
12615700
[Indexed for MEDLINE]
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