[3H]Benzo(a)pyrene metabolism in tracheal epithelial microsomes and tracheal organ cultures.

In respiratory carcinogenesis studies in Syrian golden hamsters, trachea! epithelium is a target tissue for the development of tumors induced by polynuclear aromatic hydrocarbon carcinogens. For evaluation of the capacity for metabolism of these carcinogens in this target tissue, the conversion of the carcinogen benzo(a)pyrene (BP) to polar products was studied in trachea! organ cultures and in isolated trachea! microsomes. Microsomal BP metabo lism was found to be inducible by pretreatment of tracheas with 5 JU.MBP in organ culture. The apparent K,nfor either the induced or constitutive BP monooxygenase was found to be between 1 and 2 p.m. The values of the apparent Vmaxwere 31 and 86 pmol product formed per mg microsomal protein per min for the constitutive and in duced enzymes, respectively. Isolated trachea! micro somes catalyzed the binding of [3H]BP to DMA in vitro. Analysis of metabolites produced by trachea! epithelial microsomes with high-pressure liquid chromatography showed that diols, quiñones, and phenols of BP were the major metabolic products formed during 30-min incuba tions. After 24 hrthe metabolites formed in trachea! organ cultures largely cochromatographed with tetrols, triols, and the frans-9,10-dihydro-9-10-dihydroxybenzo(a)pyrene of BP. The disparity between metabolites produced in these two systems is presumed to be related to coupled secondary metabolic reactions that occur upon prolonged incubation in the intact cells of organ cultures.