Inflammation Enhanced X-irradiation-Induced Colonic Tumorigenesis in the Min mouse

Abstract

Inflammation is potential risk factor of various human malignancies. Inflammatory bowel syndromes suchas ulcerative colitis are well known as risk factors for colon cancer. Here, we examined enhancing effects ofdextran sulfate sodium (DSS)-associated inflammation on X-irradiation induced colonic tumorigenesis in Minand wild-type (WT) mice. Animals were X-irradiated at 1.5 Gy at 5 weeks of age (at 0 experimental week) and2% DSS in drinking water was administered at 5 or 11 experimental weeks. Mice were sacrificed at 16 weeksand incidence and multiplicity of colonic tumors were assessed. Incidence of colonic tumors in Min mouse wasincreased from 33.3% to 100% (p<0.05) with X-irradiation alone, whereas no tumors were developed in WTmice. In DSS-treated Min mice, X-irradiation increased the number of colonic tumors. Total number of colonictumors was increased 1.57 times to 30.7±3.83 tumors/mouse with X-irradiation+DSS at 5 weeks comapared to19.6±2.9 in corresponding DSS alone group (p<0.05). When the duration of inflammation was compared, longerperiod of DSS effect promoted more colonic tumorigenesis. Collectively, we conclude that X-irradiation andDSS-induced inflammation act synergistically for colonic tumorigenesis.