title: Gas chromatographic analysis with chiral cyclodextrin phases reveals the enantioselective formation of hydroxylated polychlorinated biphenyls by rat liver microsomes.
abstract: Chiral PCB congeners are major components of PCB mixtures and undergo enantioselective biotransformation to hydroxylated (OH-)PCBs by cytochrome P450 enzymes. While it is known that biotransformation results in an enantiomeric enrichment of the parent PCB, it is currently unknown if OH-PCBs are formed enantioselectively. The present study screened seven commercial capillary gas chromatography columns containing modified β- or γ-cyclodextrins for their potential to separate the atropisomers of methylated derivatives of OH-PCB. The atropisomers of 3-, 4- and 5-methoxy derivatives were at least partially separated on one or more columns. A subsequent biotransformation study was performed with rat liver microsomes to assess if hydroxylated metabolites are formed enantioselectively from PCBs 91, 95, 132, and 149. The OH-PCBs were extracted from the microsomal incubations, derivatized with diazomethane and analyzed as the respective methoxylated (MeO-)PCB derivatives using selected columns. The 5-hydroxylated metabolites of PCBs 91, 95, 132, and 149 were the major metabolites, which is consistent with PCB's biotransformation by cytochrome P450 2B enzymes. All 5-hydroxylated metabolites displayed a clear, congener-specific enantiomeric enrichment. Overall, this study demonstrates for the first time that chiral PCBs, such as PCB 91, 95, 132, and 149, are enantioselectively metabolized to OH-PCBs by cytochrome P450 enzymes.
authors.affiliation: Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa 52242, United States.
authors.forename: Izabela
authors.initials: I
authors.lastname: Kania-Korwel
authors.forename: Michael W
authors.initials: MW
authors.lastname: Duffel
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lehmler
mesh_terms: D000818:Animals; D002849:Chromatography, Gas / Q000379:methods; D003505:Cyclodextrins / Q000737:chemistry; D006900:Hydroxylation; D007536:Isomerism; D008862:Microsomes, Liver / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats
chemical_list: D003505:Cyclodextrins; D011078:Polychlorinated Biphenyls