| Polychlorinated biphenyls are persistent environmental pollutants that are complete carcinogens in rodents. The carcinogenicity of PCBs is probably reflected not only in the electrophilicity of the active metabolites required for persistent in vivo DNA covalent binding, but also in their ability to redox cycle and cause increased oxidative DNA damage. The following studies are aimed at elucidating the mechanisms of genotoxicity of halogenated biphenyls.;(2) Monochloro-, dichloro- and trichlorobiphenyls in which only one ring contains chlorine substituents, were employed to determine the potency of PCBs to form DNA-adducts. These congeners were selected since it was presumed the rates of metabolism would be higher, increasing the formation of reactive metabolites. 2-chloro-, 3-chloro-, 3,4-dichloro- and 3,4,5-trichioro-biphenyl produced 1 to 3 major DNA adducts. Co-chromatographic studies with 3,4-dichlorobiphenyl DNA adducts and 3,4-dichlorobiphenyl deoxyguanosine adducts indicated that the major DNA adduct formed was deoxyguanosine derived.;(3) Nitroblue tetrazolium reduction (NBT assay) was used to detect the formation of superoxide during the enzymatic oxidation of PCB dihydroxy metabolites. The formation of O;(4) The oxidation of PCB metabolites by lactoperoxidase in the presence of calf thymus DNA resulted in a substantial increase in 8-oxodG formation. CuCl;(1) The characterization of the major reaction products of 2-(4;(5) 8-oxodG levels in liver DNA of male Sprague-Dawley rats treated with PCBs for three days was not significantly higher than control treated rats. However, pretreatment with PB-3MC for three days followed by treatment with PCBs for three days increased 8-oxodG formation in liver DNA of rats. |
