| Research Abstract |
Benzo[a]pyrene (B[a]P) induces synthesis of several cytochrome P450 enzymes in various organs of wild-type of, but not arylhydrocarbon receptor (AhR)-deficient, C57BL/6J mice. Incubation in vitro of Kanechlor (KC) 300, a polychlorinated biphenyl (PCB) mixture containing 42% chlorine, with liver microsomes of humans, rats, and mice caused decreases in the levels of PCB congeners that were extracted with n-hexane and we found that such decreases in PCB levels were more profound when liver microsomes of mice treated with B[a]P were used. PCB congeners with lower chlorine substitution were more easily decreased than those with higher chlorine substitution in the molecules. KC300, KC400 (containing 48% chlorine), and KC500 (containing 55% chlorine) were injected ip to control and B[a]P-treated AhR(+/+) mice and to control AhR(-/-) mice and the retention of PCB congeners in blood of these mice was determined by GC-MS. PCB congeners that were extracted with n-hexane were separated into 103 pe
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aks on GC-MS analysis and the residual levels of PCB congeners in the blood were determined. Again PCB congeners with lower chlorine substituion, particularly dichiorobiphenyis and several of trichiorobiphenyl isomers, were found to decrease in the blood levels more profoundly than other PCB congeners with higher chlorine substitution. Of trichlorobiphenyls examined, 2, 4, 4'- and 3, 4, 5'-trichiorobiphenyls tended to retain strongly in the blood. We also found that 2, 4, 4', 5-/2, 3, 4, 5-, 2, 3', 4, 4'-, 2, 2', 3, 6'-/2, 2', 5, 5'-/2, 3', 4, 6-, and 2, 3, 3', 4'-/2, 3, 4, 4'- were present relatively at high levels in the blood. Most of the penta- and hexachlorobiphenyls were highly retained in the blood, however, some of these PCBs decreased in the blood levels depending on the PCB structures. PCB congeners such as 2, 4, 4'-trichiorobiphenyl and 2, 3', 4, 4'-, 2, 4, 4', 5/2, 3, 4, 5-, 2, 3, 3', 4-, and 2, 3, 4, 4'-tetrachiorobiphenyls appeared to be more metabolized in AhR(+/+) mice treated with B[a]P than in control mice. These results suggest that PCB congeners that have been reported to be persistent in humans were also highly persistent in mouse blood in vivo and these AhR(+/+) and AhR(-/-) mice may be good model in the studies of PCB residues in humans. Less
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