Mismatch repair deficient mice show susceptibility to oxidative stress-induced intestinal carcinogenesis

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...

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Bibliographic Details
Published in:International journal of biological sciences 2014-01, Vol.10 (1), p.73-79
Main Authors: Piao, Jingshu, Nakatsu, Yoshimichi, Ohno, Mizuki, Taguchi, Ken-ichi, Tsuzuki, Teruhisa
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Base Pair Mismatch
Base Sequence
beta Catenin - genetics
Bromates - toxicity
Carcinogenesis
DNA Primers
DNA Repair - genetics
In Situ Nick-End Labeling
Intestinal Neoplasms - chemically induced
Intestinal Neoplasms - genetics
Intestine, Small - drug effects
Intestine, Small - pathology
Mice
Mutation
MutS Homolog 2 Protein - genetics
Oxidative Stress
Research Paper
Reverse Transcriptase Polymerase Chain Reaction
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Summary: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.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.5750