title: Mismatch repair deficient mice show susceptibility to oxidative stress-induced intestinal carcinogenesis.
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.
authors.affiliation: 1. Department of Medical Biophysics and Radiation Biology, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Jingshu
authors.initials: J
authors.lastname: Piao
authors.affiliation: 1. Department of Medical Biophysics and Radiation Biology, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Nakatsu
authors.affiliation: 1. Department of Medical Biophysics and Radiation Biology, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Ohno
authors.affiliation: 2. Department of Cancer Pathology, Institute for Clinical Research, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: 1. Department of Medical Biophysics and Radiation Biology, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Tsuzuki
mesh_terms: D000818:Animals; D017209:Apoptosis; D020137:Base Pair Mismatch; D001483:Base Sequence; D001959:Bromates / Q000633:toxicity; D063646:Carcinogenesis; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics*; D020287:In Situ Nick-End Labeling; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000235:genetics*; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D051379:Mice; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D018384:Oxidative Stress; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000235:genetics
chemical_list: D001959:Bromates; C495267:CTNNB1 protein, mouse; D017931:DNA Primers; D051176:beta Catenin; C019536:potassium bromate; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein
keywords: HNPCC; Wnt signaling pathway; cell death; mutagenesis; oxidative DNA damage