Microsomal oxidation of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) results in species-dependent chiral signatures of the hydroxylated metabolites

Xianai Wu; Austin Kammerer; Hans-Joachim Lehmler

doi:10.1021/es405433t

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Microsomal oxidation of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) results in species-dependent chiral signatures of the hydroxylated metabolites

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Microsomal oxidation of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) results in species-dependent chiral signatures of the hydroxylated metabolites

Xianai Wu, Austin Kammerer and Hans-Joachim Lehmler

Environmental science & technology, Vol.48(4), pp.2436-2444

02/18/2014

DOI: 10.1021/es405433t

PMCID: PMC3983324

PMID: 24467194

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Abstract

Chiral polychlorinated biphenyls (PCBs) display variable atropisomeric enrichment in wildlife and animal models, especially at higher trophic levels. These differences in PCBs' chiral signatures are, at least in part, due to species-dependent oxidation of PCBs to hydroxylated PCB metabolites (OH-PCBs). Here, we investigate the hypothesis that the cytochrome P450 (P450) enzyme-mediated oxidation of chiral PCBs results in species-dependent differences in the chiral signatures of OH-PCBs (i.e., the direction and extent of OH-PCBs' atropisomeric enrichment). To investigate this hypothesis, we incubated PCB 136, a representative chiral PCB, with pooled human liver microsomes (HLMs) or liver microsomes from male guinea pig, hamster, monkey, mouse, and rabbit or female dog and determined average profiles and chiral signatures of the OH-PCBs. 2,2',3,3',6,6'-Hexachlorobiphenyl-4-ol (4-136) was the major metabolite in incubations with HLMs and monkey and rabbit microsomes. 2,2',3,3',6,6'-Hexachlorobiphenyl-5-ol (5-136) was the major metabolite formed by microsomes from all other species. Both 4-136 and 5-136 were formed atropselectively in all microsomal incubations; however, the direction and extent of the atropisomeric enrichment of both OH-PCB metabolites showed considerable differences across microsomal preparations obtained from different species. These differences in OH-PCBs' atropisomeric enrichment may not only be toxicologically relevant but may also be useful to study sources and transport of OH-PCBs in the environment.

Animals

Polychlorinated Biphenyls - chemistry

Hydroxylation

Oxidation-Reduction

Species Specificity

Time Factors

Stereoisomerism

Humans

Microsomes, Liver - metabolism

Female

Male

Polychlorinated Biphenyls - metabolism

Synthesis Core

Details

Title: Subtitle: Microsomal oxidation of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) results in species-dependent chiral signatures of the hydroxylated metabolites
Creators: Xianai Wu - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa, United States
Austin Kammerer
Hans-Joachim Lehmler
Resource Type: Journal article
Publication Details: Environmental science & technology, Vol.48(4), pp.2436-2444
DOI: 10.1021/es405433t
PMID: 24467194
PMCID: PMC3983324
NLM abbreviation: Environ Sci Technol
ISSN: 0013-936X
eISSN: 1520-5851
Publisher: United States
Grant note: ES06694 / NIEHS NIH HHS P30 ES005605 / NIEHS NIH HHS R01 ES017425 / NIEHS NIH HHS P42 ES013661 / NIEHS NIH HHS ES017425 / NIEHS NIH HHS P30 ES006694 / NIEHS NIH HHS ES05605 / NIEHS NIH HHS ES013661 / NIEHS NIH HHS
Language: English
Date published: 02/18/2014
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
Record Identifier: 9984000930502771

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