Carcinogenesis Advance Access published online on August 31, 2006
Carcinogenesis, doi:10.1093/carcin/bgl157
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1 University of Karlsruhe (TH), Institute of Applied Biosciences, Section of Food Chemistry and Toxicology, Kaiserstraße 12, D-76131 Karlsruhe, Germany
* To whom correspondence should be addressed. 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 enzymes 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 intraperitoneally with PCB3 (600 µmol/kg), 4-hydroxy-PCB3 (4-HO-PCB3, 400 µmol/kg), 3-methylcholanthrene (3-MC, 300 µmol/kg, positive control), or corn oil (negative control) once per week, for 4 weeks. Animals were killed 10 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 frequency. The mutation spectrum of solvent control mutants was characterized by transitions, whereas in 3-MC-animals, transversion and frameshift mutations predominated. 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.
Received April 27, 2006
Revised August 9, 2006
Accepted August 15, 2006
CARCINOGENESIS
4-monochlorobiphenyl (PCB3) induces mutations in the livers of transgenic Fisher 344 rats
Leane Lehmann 1, Harald L. Esch 2, Patricia A. Kirby 3, Larry W. Robertson 2, and Gabriele Ludewig 2 *
2 The University of Iowa, College of Public Health, Dept. of Occupational and Environmental Health 100 Oakdale Campus, Iowa City, IA 52242-5000, USA
3 The University of Iowa, Department of Pathology, Iowa City, IA 52242, USA
Gabriele Ludewig, E-mail: gabriele-ludewig{at}uiowa.edu
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