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.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced*; D003125:Colostomy; D004247:DNA / Q000378:metabolism; D004127:Dimethylhydrazines / Q000009:adverse effects*; D008297:Male; D008763:Methylhydrazines / Q000009:adverse effects*; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats
D004127:Dimethylhydrazines; D008763:Methylhydrazines; D011506:Proteins; D012313:RNA; D004247:DNA