METABOLISM AND MACROMOLECULAR BINDING OF CARCINOGENIC AND NON-CARCINOGENIC METABOLITES OF BENZO(A)PYRENE BY HAMSTER-EMBRYO CELLS

Abstract

The metabolism and macromolecular binding of 4 metabolites of benzo(a)pyrene in hamster embryo fibroblasts was 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 (78.4-80.8% 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 (36.8-43.8% of total radioactivity). With each of the compounds, from 10-20% 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 3 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.