@article{oai:repo.qst.go.jp:00044814,
 author = {Taniguchi, Kazuki and Kakinuma, Shizuko and Tokairin, Yutaka and Arai, Masami and Kohno, Hiroyuki and Wakabayashi, Keiji and Imaoka, Tatsuhiko and Ito, Eisaku and Koike, Morio and Uetake, Hiroyuki and Nishimura, Mayumi and Yamauchi, Kazumi and Sugihara, Kenichi and Shimada, Yoshiya and 谷口 和樹 and 柿沼 志津子 and 東海林 裕 and 新井 正美 and 今岡 達彦 and 西村 まゆみ and 山内 一己 and 杉原 健一 and 島田 義也},
 issue = {1/2},
 journal = {Oncology},
 month = {Mar},
 note = {Deficiencies in DNA mismatch repair (MMR) result in replication errors within key tumor suppressor genes or oncogenes, and cause hereditary nonpolyposis colorectal cancer (HNPCC). Hematological malignancy with microsatellite instability is also associated with defective MMR, but little is known about the target genes for MMR. Objective: Inflammation bowel disease, which frequently accompanies silencing of Mlh1, plays a key role in the pathogenesis of colorectal cancers.  The interaction between inflammation and mismatch repair deficiency, however, remains unclear. The aim of this study was to determine the effect of inflammation on colorectal carcinogenesis in Mlh1-deficient mice.  Method: Inflammatory colitis was induced by brief treatment of 1% dextran sodium sulfate (DSS) in drinking water for 1 week in Mlh1 knockout (Mlh1-/-), Mlh1 heterozygous (Mlh1+/-) and wild-type (Mlh1+/+) mice at 10 weeks of age. Development of colon tumors was followed for subsequent 15 weeks and the tumors were analyzed immunohistochemically for the expression and localization of iNOS, b-catenin and p53.  Results: Male and female Mlh1-/- mice with DSS showed 63% and 44% incidence of tumors, respectively, whereas no tumors were observed in Mlh1+/- and Mlh1+/+ mice.  The mice without DSS treatment did not develop any tumors regardless of genotype.  While aberrant expression of b-catenin was not detected in colonic neoplasms, p53 and iNOs expression was increased in 100% and 77%, respectively.  These immunohistochemical changes were consistent with those of human ulcerative-colitis associated colon cancers.  Conclusion: Our results indicate that Mlh1 deficiency strongly accelerates colon carcinogenesis when combined with inflammation.  Thus the cells with Mlh1 deficiency, either inherently or colitis associated, may be at an increased risk of cancer under inflammatory conditions.},
 pages = {124--130},
 title = {Mild inflammation accelerates colon carcinogenesis in Mlh1- deficient mice},
 volume = {71},
 year = {2007}
}