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Quantitation of Benzo(a)pyrene Metabolite:DNA Adducts in Selected Hepatic and Pulmonary Cell Types Isolated from [³H]Benzo(a)pyrene-treated Rabbits

Laboratory of Pharmacology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709

Benzo(a)pyrene metabolite:deoxyribonucleoside adducts were analyzed in hepatic and pulmonary cells isolated from rabbits 24 h after i.v. administration of [³H]BP (1 mg/kg; 50 mCi/kg). The major adduct in each of the cell types analyzed was (+)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene:deoxyguanosine, but (±)-r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene:deoxyguanosine and very low levels of (-)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene-deoxyguanosine and an unidentified adduct were also observed. The level of the major adduct was similar in each of the isolated cell types and was at least as high in cells with very low cytochrome P-450-dependent monooxygenase activity (hepatic nonparenchymal cells and alveolar macrophages) as in those with higher activity (hepatocytes, alveolar type II cells, and Clara cells). The binding of benzo(a)pyrene metabolites to proteins was also determined, and again binding levels did not correlate with differences in cytochrome P-450 activity.

¹ To whom requests for reprints should be addressed.

² Present address: C. H. Best Institute, University of Toronto, Ontario, Canada, M5G 1L6.

Received 1/11/85. Revised 4/23/85. Accepted 4/25/85.