DETECTION OF PCB ADDUCTS BY THE P-32 POSTLABELING TECHNIQUE

The purpose of this study was to determine whether lower chlorinated b iphenyls would be bioactivated to electrophilic metabolites by microso mes alone or in combination with peroxidase. Monochloro- and dichlorob iphenyls were incubated with liver microsomes of rats treated with phe nobarbital and beta-naphthoflavone, an NADPH-regenerating system, and deoxyguanosine 3'-monophosphate (dGp). The resultant adducts were anal yzed by P-32-postlabeling either following microsomal incubation alone (''preoxidized'') or coupled with subsequent oxidation with horseradi sh peroxidase/H2O2 (''oxidized''). The incubation of 4-monochlorobiphe nyl (4-MCB) resulted in the formation of two minor adducts by microsom al activation alone. However, the oxidized sample showed two additiona l major adducts. Formation of the latter adducts was almost completely (>80%) inhibited when the oxidation reaction was performed in the pre sence of ascorbic acid. The other test mono- and dichlorobiphenyls als o formed 1-3 major adducts. Compared with microsomal activation alone, these adducts were enhanced after the oxidation reaction or detected only in the oxidized samples. These data suggest that (1) some adducts of the lower chlorinated biphenyls are derived from arene oxides and (2) many adducts may be formed by metabolism of the parent compounds t o catechol and p-hydroquinone species, which are oxidized to semiquino nes and/or quinones. The involvement of quinones and/or semiquinones w as supported by UV/vis spectroscopic measurements, which showed that m etabolites of 4-MCB can be oxidized to products with spectra character istic of quinones. These data raise the possibility that lower chlorin ated biphenyls may be genotoxic and may explain the fact that commerci al polychlorinated biphenyl mixtures are complete rodent carcinogens.