Murine Colonic Mucosal Metabolism and Cytotoxicity of Benzo[α]pyrene

Publisher Website
Google Scholar
Abstract
Homogenates of colonic mucosa from seven mouse strains metabolized 14C-benzo[α]pyrene (BP) to alkali-soluble and water-phase products. In those strains in which liver aryl hydrocarbon hydroxylase activity is inducible by β-naphthoflavone (β-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 β-NF 24 h before the assay. No increase in the colonic metabolism of BP was seen after β-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 β-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 β-NF afforded significant protection against this cytotoxicity.