@article{oai:repo.qst.go.jp:00047081,
 author = {Morioka, Takamitsu and Miyoshi-Imamura, Tomoko and J, Blyth Benjamin and Kaminishi, Mutsumi and Kokubo, Toshiaki and Nishimura, Mayumi and Kito, Seiji and Tokairin, Yutaka and Tani, Shusuke and Murakami-Murofushi, Kimiko and Yoshimi, Naoki and Shimada, Yoshiya and Kakinuma, Shizuko and 森岡 孝満 and Ｂｌｙｔｈ Ｂｅｎｊａｍｉｎ and 上西 睦美 and 小久保 年章 and 西村 まゆみ and 鬼頭 靖司 and 東海林 裕 and 谷 修祐 and 吉見 直己 and 島田 義也 and 柿沼 志津子},
 issue = {3},
 journal = {Cancer science},
 month = {Jan},
 note = {Genetic, physiological and environmental factors are each implicated in colorectal carcinogenesis. Mutations in the mutL homolog 1 (MLH1) gene, one of the DNA mismatch repair genes, are a main cause of hereditary colon cancer syndromes such as Lynch syndrome. Long-term chronic inflammation is also a key risk factor, responsible for colitis-associated colorectal cancer; and, radiation exposure is also known to increase colorectal cancer risk. Here, we studied the effects of radiation exposure on inflammation-induced colon carcinogenesis in DNA mismatch repair-proficient and -deficient mice. Male and female Mlh1(-/-) and Mlh1(+/+) mice were irradiated with 2 Gy X-rays at 2-weeks-old or 7-weeks-old and/or treated with 1% dextran sodium sulfate (DSS) in drinking water for 7 days at 10-weeks-old to induce mild inflammatory colitis. No colon tumors developed after X-rays and/or DSS treatment in Mlh1(+/+) mice. Colon tumors developed after DSS treatment alone in Mlh1(-/-) mice, and exposure to radiation prior to DSS treatment increased the number of tumors. Histologically, colon tumors in the mice resembled the subtype of well-to-moderately differentiated adenocarcinomas with tumor-infiltrating lymphocytes of human Lynch syndrome. Immunohistochemistry revealed that expression of both p53 and β-catenin and loss of p21 and adenomatosis polyposis coli (Apc) proteins were observed at the later stages of carcinogenesis, suggesting a course of molecular pathogenesis distinct from typical sporadic or colitis-associated colon cancer in humans. In conclusion, radiation exposure could further increase the risk of colorectal carcinogenesis induced by inflammation under the conditions of Mlh1 deficiency. This article is protected by copyright. All rights reserved.},
 pages = {217--226},
 title = {Ionizing radiation, inflammation, and their interactions in colon carcinogenesis in Mlh1-deficient mice.},
 volume = {106},
 year = {2015}
}