4-monochlorobiphenyl (PCB3) induces mutations in the livers of transgenic Fisher 344 rats

4-Monochlorobiphenyl (PCB3) is found in small amounts in commercial PCB mixtures, indoor and outdoor air, and in food. In contrast to highly chlorinated congeners that are more resistant to metabolic attack, PCB3 is more readily converted by xenobiotic-metabolizing enzy-mes to monohydroxy-PCBs and further to dihydroxy-metabolites, which can be oxidized to quinones. Our recent studies demonstrated the initiating action of PCB3 in the livers of male rats. Therefore we hypothesized that PCB3 and/or its metabolite(s) are mutagenic in rat livers in vivo. To investigate the mutagenicity and the types of mutations generated by PCB3, male Fischer 344 BigBlue rats, transgenic for the lacI gene, were injected intraperi-toneally with PCB3 (600 mmol/kg), 4-hydroxy-PCB3 (4-HO-PCB3, 400 mmol/kg), 3-methylcholanthrene (3-MC, 300 mmol/kg, positive control) and corn oil (negative control) once per week, for 4 weeks. Animals were killed 17 days after the last injection and the mutant frequency of the liver lacI gene determined. 3-MC induced a 4-fold increase of the mutant frequency of the lacI gene in the liver. The mutant frequency in PCB3-treated animals was also significantly elevated. In contrast, 4-HO-PCB3 induced a non-significant doubling of the mutant fre-quency. The mutation spectrum of solvent control mutants was characterized by transitions, whereas in 3-MC-animals, transversion and frameshift mutations predomi-nated. The PCB3-induced mutation spectrum was similar to that of the 3-MC-induced mutants. In contrast, the mutation spectrum of the 4-HO-PCB3 group hardly differed from that of the control animals. This study demonstrates for the first time the mutagenicity of a PCB in vivo