MicrosomalMetabolism of Prochiral PolychlorinatedBiphenyls Results in the Enantioselective Formation of Chiral Metabolites

摘要

Polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substituents and their metabolites exist as stable rotational isomers, or atropisomers, that are nonsuperimposable mirror images of each other. Additionally, the oxidation of certain axially prochiral PCBs, such as 2,2′,4,6′-tetrachlorobiphenyl (PCB 51) and 2,2′,4,5,6′-pentachlorobiphenyl (PCB 102), in the meta position of the symmetrically substituted phenyl ring is expected to form axially chiral hydroxylated metabolites (OH-PCBs); however, the formation of chiral OH-PCBs from prochiral PCBs has not been demonstrated experimentally. Here, we investigate if the oxidation of PCB 51 and PCB 102 by different microsomal preparations results in the formation of chiral OH-PCBs. Gas chromatographic analysis revealed that PCB 51 and PCB 102 were metabolized to 2,2′,4,6′-tetrachlorobiphenyl-3′-ol (OH-PCB 51) and 2,2′,4,5,6′-pentachlorobiphenyl-3′-ol (OH-PCB 102), respectively, by liver microsomes from male rats pretreated with different inducers; untreated male monkeys, guinea pigs, rabbits,and hamsters; and female dogs. The formation of both metabolites wasinducer- and species-dependent. Both OH-PCB 51 and OH-PCB 102 werechiral and formed enantioselectively by all microsomal preparationsinvestigated. These findings demonstrate that axially chiral PCB metabolitesare formed from axially prochiral PCB congeners, a fact that shouldbe considered when studying the environmental fate, transport, andtoxicity of OH-PCBs.