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Mutations in the <jats:italic>mutL homolog 1<\/jats:italic> (<jats:italic><jats:styled-content style=\"fixed-case\">MLH<\/jats:styled-content>1<\/jats:italic>) gene, one of the <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> mismatch repair genes, are a main cause of hereditary colon cancer syndromes such as Lynch syndrome. Long\u2010term chronic inflammation is also a key risk factor, responsible for colitis\u2010associated colorectal cancer; radiation exposure is also known to increase colorectal cancer risk. Here, we studied the effects of radiation exposure on inflammation\u2010induced colon carcinogenesis in <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> mismatch repair\u2010proficient and repair\u2010deficient mice. Male and female <jats:italic>Mlh1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> and <jats:italic>Mlh1<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup> mice were irradiated with 2\u00a0Gy X\u2010rays when aged 2\u00a0weeks or 7\u00a0weeks and\/or were treated with 1% dextran sodium sulfate (<jats:styled-content style=\"fixed-case\">DSS<\/jats:styled-content>) in drinking water for 7\u00a0days at 10\u00a0weeks old to induce mild inflammatory colitis. No colon tumors developed after X\u2010rays and\/or <jats:styled-content style=\"fixed-case\">DSS<\/jats:styled-content> treatment in <jats:italic>Mlh1<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup> mice. Colon tumors developed after <jats:styled-content style=\"fixed-case\">DSS<\/jats:styled-content> treatment alone in <jats:italic>Mlh1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, and exposure to radiation prior to <jats:styled-content style=\"fixed-case\">DSS<\/jats:styled-content> treatment increased the number of tumors. Histologically, colon tumors in the mice resembled the subtype of well\u2010to\u2010moderately differentiated adenocarcinomas with tumor\u2010infiltrating lymphocytes of human Lynch syndrome. Immunohistochemistry revealed that expression of both p53 and \u03b2\u2010catenin and loss of p21 and adenomatosis polyposis coli proteins were observed at the later stages of carcinogenesis, suggesting a course of molecular pathogenesis distinct from typical sporadic or colitis\u2010associated colon cancer in humans. In conclusion, radiation exposure could further increase the risk of colorectal carcinogenesis induced by inflammation under the conditions of <jats:italic>Mlh1<\/jats:italic> deficiency.<\/jats:p>","DOI":"10.1111\/cas.12591","type":"journal-article","created":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T05:35:37Z","timestamp":1419226537000},"page":"217-226","source":"Crossref","is-referenced-by-count":23,"title":["Ionizing radiation, inflammation, and their interactions in colon carcinogenesis in <i>Mlh1\u2010<\/i>deficient mice"],"prefix":"10.1111","volume":"106","author":[{"given":"Takamitsu","family":"Morioka","sequence":"first","affiliation":[{"name":"Radiation Effect Accumulation and Prevention Project Fukushima Project Headquarters National Institute of Radiological Sciences Chiba Japan"},{"name":"Radiobiology for Children's Health Program Research Center for Radiation Protection National Institute of Radiological Sciences Chiba 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