Journal article
OXIDATION OF POLYCHLORINATED BIPHENYLS BY LIVER TISSUE SLICES FROM PHENOBARBITAL-PRETREATED MICE IS CONGENER-SPECIFIC AND ATROPSELECTIVE
Chemical research in toxicology, Vol.26(11), pp.1642-1651
11/18/2013
DOI: 10.1021/tx400229e
PMCID: PMC3857157
PMID: 24107130
Abstract
Mouse models are powerful tools to study the developmental neurotoxicity of polychlorinated biphenyls (PCBs); however, studies of the oxidation of chiral PCB congeners to potentially neurotoxic hydroxylated metabolites (OH-PCBs) in mice have not been reported. Here we investigate the atropselective oxidation of chiral PCB 91 (2,2',3,4',6-pentachlorobiphenyl), PCB 95 (2,2',3,5',6-pentachlorobiphenyl), PCB 132 (2,2',3,3',4,6'-hexachlorobiphenyl), PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl) and PCB 149 (2,2',3,4',5',6-hexachlorobiphenyl) to OH-PCBs in liver tissue slices prepared from female mice. The metabolite profile of PCB 136 typically followed the rank order 5-OH-PCB > 4-OH-PCB > 4,5-OH-PCB, and metabolite levels increased with PCB concentration and incubation time. A similar OH-PCB profile was observed with the other PCB congeners, with 5-OH-PCB:4-OH-PCB ratios ranging from 2 to 12. More 5-OH-PCB 136 was formed in liver tissue slices obtained from animals pretreated with phenobarbital (P450 2B inducer) or, to a lesser extent, dexamethasone (P450 2B and 3A enzyme inducer) compared to tissue slices prepared from vehicle-pretreated animals. The apparent rate of 5-OH-PCBs formation followed the approximate rank order PCB 149 > PCB 91 > PCB 132 ~ PCB 136 > PCB 95. Atropselective gas chromatography revealed a congener-specific atropisomeric enrichment of major OH-PCB metabolites. Comparison of our results with published OH-PCB patterns and chiral signatures (i.e., the direction and extent of the atropisomeric enrichment) from rat liver microsomal revealed drastic differences between both species, especially following induction of P450 2B enzymes. These species differences in the metabolism of chiral PCBs should be considered in developmental neurotoxicity studies of PCBs.
Details
- Title: Subtitle
- OXIDATION OF POLYCHLORINATED BIPHENYLS BY LIVER TISSUE SLICES FROM PHENOBARBITAL-PRETREATED MICE IS CONGENER-SPECIFIC AND ATROPSELECTIVE
- Creators
- Xianai Wu - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242Michael Duffel - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242Hans-Joachim Lehmler - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Chemical research in toxicology, Vol.26(11), pp.1642-1651
- DOI
- 10.1021/tx400229e
- PMID
- 24107130
- PMCID
- PMC3857157
- NLM abbreviation
- Chem Res Toxicol
- ISSN
- 0893-228X
- eISSN
- 1520-5010
- Grant note
- P42 ES013661 || ES / National Institute of Environmental Health Sciences : NIEHS P30 ES005605 || ES / National Institute of Environmental Health Sciences : NIEHS R01 ES017425 || ES / National Institute of Environmental Health Sciences : NIEHS
- Language
- English
- Date published
- 11/18/2013
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984001076902771
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