Murine colonic mucosal metabolism and cytotoxicity of benzo [alpha] pyrene.
Homogenates of colonic mucosa from seven mouse strains metabolized 14 C-benzol [alpha] pyrene (BP) to alkali-soluble and water-phase products. In those strains in which liver aryl hydrocarbon hydroxylase activity is inducible by beta-naphthoflavone (beta-NF), the C57Bl/6, BALB/c, C3H and random-bred Swiss CD-1, colonic metabolism of BP was also induced by intraperitoneal treatment with 150 mg/kg beta-NF 24 h before assay. No increase in the colonic metabolism of BP was seen after beta-NF treatment of the noninducible strains, AKR, DBA and SWR. A detailed study of the products formed was carried out with C57BL/6 male mice. High-performance liquid-chromatography analysis of the products of BP metabolism revealed that phenolic derivatives predominated, but that a small percentage of the BP was converted into the proximate carcinogen, the BP-7,8-diol. Addition of uridine 5'-diphosphoglucuronic acid to the incubation mixture caused an increase in total product formation and a shift from alkali-soluble to water-phase products. Of the water-phase products formed by beta-NF-induced colonic mucosal homogenates, about 40% were nondialyzable and associated with precipitable material. In a study of the cellular effects of BP on the colonic mucosa, intrarectal administration of 1 mg BP had a significant cytotoxic effect, as indicated by the number of pyknotic cells and 3H-thymidine-labeling index, and prior treatment with beta-NF afforded significant protection against this cytotoxicity.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001580:Benzopyrenes / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009281:Naphthalenes / Q000494:pharmacology; D013045:Species Specificity
D001580:Benzopyrenes; D009281:Naphthalenes; D001189:Aryl Hydrocarbon Hydroxylases