Benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene metabolism and DNA adduct formation in primary cultures of hamster epidermal cells.
Primary cultures of hamster epidermal cells exposed to hydrocarbon, 1 microgram/ml, rapidly metabolized [3H]benzo(a)pyrene and [14C]7,12-dimethylbenz(a)anthracene to ethyl acetate:acetone- and water-soluble metabolites. By 24 hr, only 13.6% of the organic solvent-soluble radioactivity recovered in the medium was unchanged [3H]benzo(a)pyrene, and only 5.9% was unchanged [14C]7,12-dimethylbenz(a)anthracene. With both hydrocarbons, the major water-soluble metabolites found extracellularly were conjugated with glucuronic acid; these were primarily phenolic derivatives. Metabolites cochromatographing with 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene or trans-3,4-dihydro-3,4-dihydroxy-7,12-dimethylbenz(a)anthracene were not detectable in high-pressure liquid chromatographic profiles of organic solvent-soluble intracellular and extracellular metabolites. However, analysis of [3H]benzo(a)pyrene: and [3H]7,12-dimethylbenz(a)anthracene: DNA adducts indicated that these putative proximate carcinogenic metabolites were formed in these cells and subsequently metabolized to DNA-binding products. The results suggest that metabolic incompetence may not be an explanation for the relative resistance of the hamster to epidermal carcinogenesis by polycyclic hydrocarbons.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D008647:Mesocricetus
D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA