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Benzo(a)pyrene and 7,12-Dimethylbenz(a)anthracene Metabolism and DNA Adduct Formation in Primary Cultures of Hamster Epidermal Cells¹

The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104

Primary cultures of hamster epidermal cells exposed to hydrocarbon, 1 µg/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.

¹ Research was supported in part by USPHS Grants CA-21778, CA-10815, and CA-30446 from the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed.

³ Present address: Merck Institute for Therapeutic Research, West Point, Pa. 19486.

Received 6/21/82. Accepted 10/12/82.