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Enantiomeric Enrichment of 2,2′,3,3′,6,6′-Hexachlorobiphenyl (PCB 136) in Mice After Induction of CYP Enzymes

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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, β-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.

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Acknowledgments

We thank Dr. Regine Garcia Boy for assistance with the animal procedures, Collin Just for help with the GC analysis, Holly Moriarty and Allison Smith for help with the analytical work, and Dr. Botond Banfi for use of his metabolism cages. This research was supported by Grants ES05605, ES013661, and ES012475 from the National Institute of Environmental Health Sciences, NIH, and Major Research Instrumentation Grant BES-0420378 form the National Science Foundation.

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Authors and Affiliations

  1. Department of Occupational and Environmental Health, University of Iowa, College of Public Health, 100 Oakdale Campus, 114 IREH, Iowa City, IA, 52242, USA

    Izabela Kania-Korwel, Wei Xie, Larry W. Robertson & Hans-Joachim Lehmler

  2. Department of Environmental Chemistry and Technology, University of Silesia, Szkolna 9, 40-006, Katowice, Poland

    Izabela Kania-Korwel

  3. Department of Civil and Environmental Engineering, University of Iowa, Iowa City, IA, 52242, USA

    Keri C. Hornbuckle

  4. The Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA, 52242, USA

    Larry W. Robertson & Hans-Joachim Lehmler

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  1. Izabela Kania-Korwel
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  2. Wei Xie
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  3. Keri C. Hornbuckle
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  4. Larry W. Robertson
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  5. Hans-Joachim Lehmler
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Correspondence to Hans-Joachim Lehmler.

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Kania-Korwel, I., Xie, W., Hornbuckle, K.C. et al. Enantiomeric Enrichment of 2,2′,3,3′,6,6′-Hexachlorobiphenyl (PCB 136) in Mice After Induction of CYP Enzymes. Arch Environ Contam Toxicol 55, 510–517 (2008). https://doi.org/10.1007/s00244-007-9111-4

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  • DOI: https://doi.org/10.1007/s00244-007-9111-4

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