Rat colon mucosa microsomes contain a competent mixed function oxidase system that hydroxylates the N-methyl drugs benzphetamine and ethylmorphine, the 0-alkyl drugs p-nitroanisole and p-nitrophenetole and the polycyclic carcinogen benzo[a]pyrene. The colon system's hydroxylation activities can be selectively induced by pretreatment with phenobarbital or fi-naphthoflavone and can be selectively inhibited by SKF-525A or 7,8-benzoflavone. The colon microsomal system has been solubilized with the non-ionic detergent Renex 690 and resolved by column chromatography into its components cytochrome P-450 and cytochrome P-450 reductase. Colon cytochrome P-450 and cytochrome P-450 reductase can be recombined to reconstitute hydroxylation activity. The colon system is also able to activate carcinogens to mutagenic metabolites as demonstrated in the Ames test system. In addition, the activity of the colon system is markedly increased by pretreatment with gastrointestinal hormones.
Cancer 451060-1065. 1980.
MAJOR FOCUS OF T H E STUDY of large bowel car-
A cinogenesis has been the elucidation of the manner of presentation to the colon of activated carcinogens. Activation by the fecal flora of precarcinogens in the diet has been suggested as a pathway to colon c a n ~e r . ~~. ~~ Wynder and co-workers have also shown through epidemiological studies that the incidence of colon cancer is associated with the total fat content of the diet.33,35 They have proposed that the fat content of the diet influences the fecal bacterial content and composition and that also in this way fat content may affect colon c a r c i n o g e n e ~i s . ~~~~~ Several laboratories12.22x23 have shown that anaerobic bacteria are more predominant than aerobic bacteria in diets with a high fat content. Thus, it has also been posited" that the anaerobic fecal bacteria, increased in content by dietary fat, may activate dietary precarcinogens. This contention, however, has been questi0ned.