Induction of colon mucosal beta-glucuronidase production as a mechanism for 1,2-dimethylhydrazine colon carcinogenesis.
Although early studies in germ-free rats showed almost complete dependence on dimethylhydrazine (DMH) colon carcinogenesis upon the presence of colon bacteria, no adequate explanation was given for the 20% tumor incidence observed in germ-free animals. Bacterial activation of liver microsomal products releasing active proximate carcinogens has been the accepted reason for the exquisite specificity DMH has for the colon. Recent work, including the present study, show the colon mucosa is capable of metabolizing carcinogens and activating conjugating forms metabolized in the liver independent of the intestinal microflora. Mucosal beta-glucuronidase production was assayed in coded, scraped mucosa samples from the duodenum/jejunum, ileum, right colon, and left colon of normal and DMH-treated rats. Normal mucosal beta-glucuronidase production was highest in the left colon followed by the right colon, duodenum, and ileum, respectively. Enzyme production in the left colon was significantly increased 24 hours after injection of 25 mg/kg body weight DMH. No elevation was seen in other mucosal samples. Metabolism of DMH to oxidated forms conjugated to glucuronic acid is well established. Thus, this study offers a possible role for carcinogen, induction of a metabolic enzyme in its target tissue.
D000818:Animals; D003106:Colon / Q000201:enzymology*; D003110:Colonic Neoplasms / Q000139:chemically induced*; D004127:Dimethylhydrazines / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000201:enzymology*; D008297:Male; D008763:Methylhydrazines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004127:Dimethylhydrazines; D008763:Methylhydrazines; D005966:Glucuronidase