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Metabolism and Macromolecular Binding of Carcinogenic and Noncarcinogenic Metabolites of Benzo(a)pyrene by Hamster Embryo Cells¹

Biology Division, Oak Ridge National Laboratory [G. M. C., M. C. M., J. K. S.], and The University of Tennessee-Oak Ridge Graduate School of Biomedical Sciences [C. J. M.], Oak Ridge, Tennessee 37830

The metabolism and macromolecular binding of four metabolites of benzo(a)pyrene in hamster embryo fibroblasts has been studied. Two noncarcinogenic phenolic derivatives, 3-hydroxybenz(a)pyrene and 9-hydroxybenzo(a)pyrene, are rapidly metabolized, primarily to their respective glucuronic acid conjugates and other H₂O-soluble conjugates (78.4 to 80.8% of total radioactivity). Water-soluble conjugates were also formed from the carcinogenic phenol, 2-hydroxybenzo(a)pyrene, and from 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, but in lower amounts (36.8 to 43.8% of total radioactivity). With each of the compounds, from 10 to 20% of the radioactivity was converted to ethyl acetate-soluble metabolites. The amount of unmetabolized 2-hydroxybenzo(a)pyrene recovered intracellularly was 20-fold higher than that recovered in incubations with the other phenols.

Covalent binding to nuclear macromolecules was monitored after isopyknic separation. Binding of the three phenols tested was similar and was lower than the binding of benzo(a)pyrene to nuclear DNA, RNA, and protein. In contrast to the results with the monohydroxybenzo(a)pyrenes, high levels of covalent binding were observed with 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene; binding to DNA was 8-fold higher (315 pmol bound per mg DNA) than binding of benzo(a)pyrene to DNA.

¹ Research sponsored jointly by the National Cancer Institute under Interagency Agreement (4-5-63) and the Office of Health and Environmental Research, Unites States Department of Energy, under Contract W-7405-eng-26 with the Union Carbide Corporation.

² Permanent address: Department of Biochemistry, University of Surrey, Guildford, Surrey, England GU2 5XH.

³ Postdoctoral Fellow supported by Grant CA 05296 from the National Cancer Institute to the University of Tennessee-Oak Ridge Biomedical Graduate School Carcinogenesis Training Grant.

⁴ To whom requests for reprints should be addressed.

Received 8/13/79. Accepted 10/19/79.