2,2′,3,5′,6-PENTACHLOROBIPHENYL (PCB 95) AND ITS HYDROXYLATED METABOLITES ARE ENANTIOMERICALLY ENRICHED IN FEMALE MICE

Izabela Kania-Korwel; Christopher D Barnhart; Marianna Stamou; Kim M Truong; Mohammed H.M.E El-Komy; Pamela J Lein; Peter Veng-Pedersen; Hans-Joachim Lehmler

doi:10.1021/es302810t

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2,2′,3,5′,6-PENTACHLOROBIPHENYL (PCB 95) AND ITS HYDROXYLATED METABOLITES ARE ENANTIOMERICALLY ENRICHED IN FEMALE MICE

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2,2′,3,5′,6-PENTACHLOROBIPHENYL (PCB 95) AND ITS HYDROXYLATED METABOLITES ARE ENANTIOMERICALLY ENRICHED IN FEMALE MICE

Izabela Kania-Korwel, Christopher D Barnhart, Marianna Stamou, Kim M Truong, Mohammed H.M.E El-Komy, Pamela J Lein, Peter Veng-Pedersen and Hans-Joachim Lehmler

Environmental science & technology, Vol.46(20), pp.11393-11401

10/16/2012

DOI: 10.1021/es302810t

PMCID: PMC3475189

PMID: 22974126

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Abstract

Epidemiological and laboratory studies link polychlorinated biphenyls and their metabolites to adverse neurodevelopmental outcomes. Several neurotoxic PCB congeners are chiral and undergo enantiomeric enrichment in mammalian species, which may modulate PCB developmental neurotoxicity. This study measures levels and enantiomeric enrichment of PCB 95 and its hydroxylated metabolites (OH-PCBs) in adult female C57Bl/6 mice following subchronic exposure to racemic PCB 95. Tissue levels of PCB 95 and OH-PCBs increased with increasing dose. Dose-dependent enantiomeric enrichment of PCB 95 was observed in brain and other tissues. OH-PCBs also displayed enantiomeric enrichment in blood and liver, but were not detected in adipose and brain. In light of data suggesting enantioselective effects of chiral PCBs on molecular targets linked to PCB developmental neurotoxicity, our observations highlight the importance of accounting for PCB and OH-PCB enantiomeric enrichment in the assessment of PCB developmental neurotoxicity.

hydroxylated PCB metabolites

polychlorinated biphenyls

Atropisomers

cytochrome P-450 enzyme

dose-response

qPCR

atropisomeric enrichment

Details

Title: Subtitle: 2,2′,3,5′,6-PENTACHLOROBIPHENYL (PCB 95) AND ITS HYDROXYLATED METABOLITES ARE ENANTIOMERICALLY ENRICHED IN FEMALE MICE
Creators: Izabela Kania-Korwel - Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa
Christopher D Barnhart - Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa
Marianna Stamou - Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa
Kim M Truong - Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa
Mohammed H.M.E El-Komy - Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa
Pamela J Lein - Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa
Peter Veng-Pedersen - Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa
Hans-Joachim Lehmler - Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Environmental science & technology, Vol.46(20), pp.11393-11401
DOI: 10.1021/es302810t
PMID: 22974126
PMCID: PMC3475189
NLM abbreviation: Environ Sci Technol
ISSN: 0013-936X
eISSN: 1520-5851
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: 10/16/2012
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Iowa Superfund Research Program
Record Identifier: 9984001085902771

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