Effects of Aroclar 1254-induced rat liver S-9 fraction on benzo[a]pyrene-mediated DNA damage and benzo[a]pyrene metabolism in cultured human skin fibroblasts

Incubation of cultured normal human skin fibroblasts with benzo[a]pyrene (B[a]P) resulted in covalent binding of B[a]P to protein, RNA and DNA. B[a]P adduct formation was increased when the cultured cells were also treated with the 9,000 g hepatic microsomal supernatant (S-9) fraction from rats pretreated with Aroclor 1254, a commercial preparation of polychlorinated biphenyls (PCBs). Comparison with control experiments which included the incubation with corn oil-induced S-9 fraction indicated that the enhanced B[a]P-adduct formation in the host cells was related to the induction of hepatic NADPH-dependent microsomal monooxygenase activity by Aroclor 1254 in the S-9 fraction. Parallel experiments showed that this Aroclor-induced enzymic activity was responsible for B[a]P-mediated DNA damage as measured by unscheduled DNA synthesis (UDS) in the cells. Similarly, administration of rat hepatic S-9 induced by 3-methylcholanthrene (MC) and phenobarbitone (PB) caused B[a]P-mediated DNA damage in cultured human skin fibroblasts.