Mutagenicity of 3-methylcholanthrene, PCB3, and 4-OH-PCB3 in the lung of transgenic BigBlue® rats

Recent findings of high levels of predominantly lower chlorinated biphenyls in indoor and outdoor air open the question of possible health consequences. Lower chlorinated biphenyls are more readily metabolized to reactive and potentially harmful intermediates, acting as mutagens and cancer initiators. The goal of this study was to assess the mutagenicity of PCB3 in the lungs of rats. Male BigBlue® 334 Fisher transgenic rats, which carry the bacterial lacI gene as a target of mutagenicity, were given intraperitoneal injections of corn oil, 3-methylcholanthrene (3-MC, positive control), 4-monochlorobiphenyl (PCB3) or its metabolite 4-hydroxy-PCB3 (4-OH-PCB3) weekly for 4 weeks. Lung tissue was harvested to determine mutant frequencies, mutation spectra, and pathological changes. 3-MC caused a 11-fold increase in mutant frequency and an increase in transversion type mutations; a very early occurrence of this type of mutation was previously identified in Ki-ras oncogenes of lung tumors from 3-MC exposed mice. The two-fold increase in the mutant frequency after treatment with PCB3 and 4-OH-PCB3 was not statistically significant, but a shift in the mutation spectra, especially with PCB3, and an increase in mutations outside of the hotspot region for spontaneous mutations (bp 1–400), suggest that PCB3 and possibly 4-OH-PCB3 are mutagenic in the rat lung.