Experimental colon carcinogenesis is facilitated by endogenous factors in the intestinal contents

The theory that endogenous factors in the intestinal contentsmay be pathogenic during large bowel carcinogenesis was testedin the dimethylhydrazine (DMH)-induced rat colon cancer model.Thirty female Wistar rats, each serving as their own control,had a surgical transection of the proximal colon with reanastomosisto the rectum, thereby excluding part of the colon from faecalcontact. All rats then received a course of DMH (40 mg/kg bodywt/wk s.c. for 10 weeks) while fed on Vivonex. This diet wasselected because it lacks known exogenous (dietary) cocarcinogens.It also produces mucosal atrophy in functioning (proximal) colon,to parallel the disuse atrophy induced in the defunctioned (distal)colon. Animals remained on the diet throughout the experimentand were killed when moribund or at 40 weeks. At necropsy, theanatomical distribution, number, size and histological typeof colon tumours were compared between functioning and defunctionedcolonic segments within the same animal. At autopsy, there weresignificantly fewer colon tumours in the defunctioned segment(P < 0.005). Furthermore, there were significantly fewercarcinomas (P <0.005) and fewer tumours >1 cm diameter(P <0.01) in this segment. The data indicate that endogenousfactors in the intestinal contents facilitate chemically-inducedcolon carcinogenesis. Luminal nutrition may be implicated.