International Journal of Biological Sciences

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Int J Biol Sci 2014; 10(1):73-79. doi:10.7150/ijbs.5750

Research Paper

Mismatch Repair Deficient Mice Show Susceptibility to Oxidative Stress-Induced Intestinal Carcinogenesis

Jingshu Piao1, Yoshimichi Nakatsu1, Mizuki Ohno1, Ken-ichi Taguchi2, Teruhisa Tsuzuki1 ✉

1. Department of Medical Biophysics and Radiation Biology, Graduate School of Medical Sciences, Kyushu University,
2. Department of Cancer Pathology, Institute for Clinical Research, National Kyushu Cancer Center, Fukuoka, Japan

Abstract

We have previously established an experimental system for oxidative DNA damage-induced tumorigenesis in the small intestine of mice. To elucidate the roles of mismatch repair genes in the tumor suppression, we performed oxidative DNA damage-induced tumorigenesis experiments using Msh2-deficient mice. Oral administration of 0.2% Potassium Bromate, KBrO3, effectively induced epithelial tumors in the small intestines of Msh2-deficient mice. We observed a 22.5-fold increase in tumor formation in the small intestines of Msh2-deficient mice compared with the wild type mice. These results indicate that mismatch repair is involved in the suppression of oxidative stress-induced intestinal tumorigenesis in mice. A mutation analysis of the Ctnnb1 gene of the tumors revealed predominant occurrences of G:C to A:T transitions. The TUNEL analysis showed a decreased number of TUNEL-positive cells in the crypts of small intestines from the Msh2-deficient mice compared with the wild type mice after treatment of KBrO3. These results suggest that the mismatch repair system may simultaneously function in both avoiding mutagenesis and inducing cell death to suppress the tumorigenesis induced by oxidative stress in the small intestine of mice.

Keywords: HNPCC, oxidative DNA damage, Wnt signaling pathway, mutagenesis, cell death

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How to cite this article:
Piao J, Nakatsu Y, Ohno M, Taguchi Ki, Tsuzuki T. Mismatch Repair Deficient Mice Show Susceptibility to Oxidative Stress-Induced Intestinal Carcinogenesis. Int J Biol Sci 2014; 10(1):73-79. doi:10.7150/ijbs.5750. Available from http://www.ijbs.com/v10p0073.htm