Colostomy closure promotes cell proliferation and dimethylhydrazine-induced carcinogenesis in rat distal colon.

The influence of adaptive cell proliferation on colonic carcinogenesis was studied in male Fischer rats with a defunctioning transverse colostomy that was closed 4 wk later. Control observations were made in other rats after colonic transection, repeated at 4 wk, after laparotomy alone, or after permanent colostomy. Tumors were induced by 1,2-dimethylhydrazine (total dose, 300 mg/kg) over 11 wk, starting 2 days after the second operation. After creation of the colostomy, amounts of protein, RNA, and DNA in the distal colon halved in 4 wk (p less than 0.001), but returned to normal 7 days after restoration of colonic continuity. This reactive hyperplasia promoted the development of distal colonic carcinomas, as compared with rats having repeated transection of the bowel (incidence 32% vs. 6%; p less than 0.03). Although the amounts of protein and nucleic acid in the proximal colon were unchanged by transverse colostomy, values increased by 18%-59% 4 wk after colostomy closure (p = 0.05-0.002); nonetheless, the yield of tumors in this segment was unaltered. Suture-line cancers were commoner after repeat transection than after colostomy closure (76% vs. 39%; p less than 0.01). These data confirm the promotional effect of increased cell proliferation on intestinal carcinogenesis.