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

Abstract

The theory that endogenous factors in the intestinal contents may be pathogenic during large bowel carcinogenesis was tested in 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 reanastomosis to the rectum, thereby excluding part of the colon from faecal contact. All rats then received a course of DMH (40 mg/kg body wt/wk s.c. for 10 weeks) while fed on Vivonex. This diet was selected 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 experiment and were killed when moribund or at 40 weeks. At necropsy, the anatomical distribution, number, size and histological type of colon tumours were compared between functioning and defunctioned colonic segments within the same animal. At autopsy, there were significantly fewer colon tumours in the defunctioned segment (P less than 0.005). Furthermore, there were significantly fewer carcinomas (P less than 0.005) and fewer tumours greater than 1 cm diameter (P less than 0.01) in this segment. The data indicate that endogenous factors in the intestinal contents facilitate chemically-induced colon carcinogenesis. Luminal nutrition may be implicated.