Abstract
Inflammation is potential risk factor of various human malignancies. Inflammatory bowel syndromes such as ulcerative colitis are well known as risk factors for colon cancer. Here, we examined enhancing effects of dextran sulfate sodium (DSS)-associated inflammation on X-irradiation induced colonic tumorigenesis in Min and wild-type (WT) mice. Animals were X-irradiated at 1.5 Gy at 5 weeks of age (at 0 experimental week) and 2% DSS in drinking water was administered at 5 or 11 experimental weeks. Mice were sacrificed at 16 weeks and incidence and multiplicity of colonic tumors were assessed. Incidence of colonic tumors in Min mouse was increased from 33.3% to 100% (p<0.05) with X-irradiation alone, whereas no tumors were developed in WT mice. In DSS-treated Min mice, X-irradiation increased the number of colonic tumors. Total number of colonic tumors was increased 1.57 times to 30.7±3.83 tumors/mouse with X-irradiation+DSS at 5 weeks comapared to 19.6±2.9 in corresponding DSS alone group (p<0.05). When the duration of inflammation was compared, longer period of DSS effect promoted more colonic tumorigenesis. Collectively, we conclude that X-irradiation and DSS-induced inflammation act synergistically for colonic tumorigenesis.
Highlights
Inflammation has been widely known as strong risk and promoting factor of carcinogenesis (Balkwill and Mantovani, 2001) in various types of human cancers (Ohshima et al, 2003)
Incidence of colonic tumors in Male C57BL/6J-ApcMin/J (Min) mouse was increased from 33.3% to 100% (p
When Groups Min-A and Min-C were compared in Min mice, incidence of Group C (100%) was higher than that of Group A (33.3%), proving the aggravating effect of X-irradiation especially in Min mice (p
Summary
Inflammation has been widely known as strong risk and promoting factor of carcinogenesis (Balkwill and Mantovani, 2001) in various types of human cancers (Ohshima et al, 2003). Dextran sulfate sodium (DSS) (Okayasu et al, 1990) showed powerful tumor promoting effect in murine colonic carcinogenesis models initiated with azoxymethane (AOM) (Tanaka et al, 2003), 1,2-dimethylhydrazine (DMH) (Kohno et al, 2005), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (Tanaka et al, 2005). FAP is caused by mutation in the adenomatous polyposis coli (APC) tumor suppressor gene (Powell et al, 1993). Min (multiple intestinal neoplasia) mouse is a murine model of human FAP (Moser et al, 1990), which has nonsense mutation at codon 850 in Apc gene (Su et al, 1992). Other colonic carcinogens including PhIP (Steffensen et al, 1997) and AOM (Paulsen et al, 2003) increased intestinal tumors. Inflammatory stimuli by DSS strongly induced colonic neoplasia in Min mice (Tanaka et al, 2006)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
