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Benzo(a)pyrene Metabolism in Bovine Aortic Endothelial and Bovine Lung Fibroblast-like Cell Cultures¹

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

The metabolism of [³H]benzo(a)pyrene ([³H]BP) in bovine aortic endothelial and bovine lung fibroblast-like cells in vitro was investigated. Both cell types metabolized BP to organic solvent-extractable and water-soluble metabolites. The major organic solvent-extractable metabolites were 9-hydroxybenzo(a)pyrene and 3-hydroxybenzo(a)pyrene; 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, 9,10-dihydro-9,10-dihydroxybenzo(a)pyrene, and BP quinones were also formed. No glucuronide or sulfate conjugates of BP metabolites were detected. When exposed to [³H]-3-hydroxybenzo(a)pyrene, both cell types metabolized this phenol to water-soluble derivatives, probably through oxidation rather than conjugation of the molecule.

These results demonstrate that endothelial cells metabolize BP to a proximate carcinogenic derivative, the 7,8-dihydrodiol. Thus, efforts to predict the biological effects of hydrocarbons on an organism must take into account possible metabolic activation by endothelial cells as well as by other target tissues. The formation of unconjugated, phenolic hydrocarbon derivatives by bovine cells suggests their use as a model system for studying the contribution of phenols to the induction of biological effects by hydrocarbons.

¹ This research was supported in part by Grants CA 21778 and CA 19948 from the Department of Health, Education, and Welfare.

² To whom requests for reprints should be addressed, at The Wistar Institute.

³ Present address: Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Ind. 47907.

⁴ Predoctoral trainee supported by Grant 1T32-CA 09171 from the Department of Health, Education, and Welfare to The Wistar Institute.

Received 11/29/79. Accepted 2/13/80.

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