title: Enantiomeric enrichment of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in mice after induction of CYP enzymes.
abstract: Several PCB congeners, present in commercial PCB formulations, are chiral. These PCBs can undergo enantiomeric enrichment in many animal species and in humans due to currently uncharacterized enantioselective biotransformation processes. To investigate if certain cytochrome P-450 enzymes (CYPs), such as CYP2B's, are responsible for this enantiomeric enrichment, we investigated the enantioselective disposition of (+/-)-PCB 136 in female mice after induction of different CYP enzymes by pretreatment with corn oil alone, beta-naphthoflavone (CYP1A's), phenobarbital (CYP2B's), or dexamethasone (2B's and 3A's), followed by oral PCB administration. PCB 136 levels were significantly lower in phenobarbital- and, to a lesser extent, in dexamethasone-pretreated animals, presumably due to the induction of PCB 136 metabolizing enzymes. Although (+)-PCB 136 was enriched in all tissues, none of the pretreatments altered the enantioselective disposition of PCB 136 in a manner that suggests a particular CYP subfamily as the cause of the enrichment of (+)-PCB 136. Fecal PCB levels and enantiomeric fraction values changed over time in a manner consistent with slower digestive motility in the mice pretreated with phenobarbital and dexamethasone. Overall, this study does not support the hypothesis that metabolism by CYP2B enzymes is responsible for the enrichment of (+)-PCB 136 in mice.
authors.affiliation: Department of Occupational and Environmental Health, University of Iowa, College of Public Health, 100 Oakdale Campus, 114 IREH, Iowa City, IA 52242, USA.
authors.forename: Izabela
authors.initials: I
authors.lastname: Kania-Korwel
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Keri C
authors.initials: KC
authors.lastname: Hornbuckle
authors.forename: Larry W
authors.initials: LW
authors.lastname: Robertson
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lehmler
mesh_terms: D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; C010498:2,3,6,2',3',6'-hexachlorobiphenyl