Assessment of the disposition of chiral polychlorinated biphenyls in female mdr 1a/b knockout versus wild-type mice using multivariate analyses

Bartłomiej Milanowski; Janina Lulek; Hans-Joachim Lehmler; Izabela Kania-Korwel

doi:10.1016/j.envint.2009.10.007

Back

Assessment of the disposition of chiral polychlorinated biphenyls in female mdr 1a/b knockout versus wild-type mice using multivariate analyses

Journal article

Open access

Peer reviewed

Assessment of the disposition of chiral polychlorinated biphenyls in female mdr 1a/b knockout versus wild-type mice using multivariate analyses

Bartłomiej Milanowski, Janina Lulek, Hans-Joachim Lehmler and Izabela Kania-Korwel

Environment international, Vol.36(8), pp.884-892

2010

DOI: 10.1016/j.envint.2009.10.007

PMCID: PMC2891895

PMID: 19923000

Files and links (1)

url

https://doaj.org/article/10e628a0f476421db5315c23f46e6ecdView

Open Access

Abstract

Polychlorinated biphenyls (PCBs) are present in the environment as complex mixtures, which make it challenging to identify PCB congeners that may be subject to active transport processes. Here we employ a transgenic mouse model in combination with multivariate analyses to investigate if chiral PCBs 91, 95, 132, 136, 149, 174, 176 and 183 are subject to active (enantioselective) transport by multidrug resistance (MDR) transporters. A synthetic PCB mixture containing these congeners was administered orally to female FVB or mdr1a/1b knockout mice. Due to the short half-life of chiral PCB congeners, mice were euthanized after 24 h and PCB concentrations and enantiomeric fractions were determined in selected tissues and excreta. Principal component analysis did not reveal differences between wild-type and mdr1a/1b knockout mice. However, Hotelling T 2-test revealed significantly lower PCB concentrations and a more pronounced enantiomeric enrichment in the adipose tissue of mdr1a/1b knockout mice. These differences are due to higher body weights and higher fecal fat contents of mdr1a/1b knockout mice. Analysis of the enantiomeric fractions of PCBs 91, 95, 136, 149 and 174 showed a significant enantiomeric enrichment for all five congeners in wild-type and mdr1a/1b knockout mice. Overall, by studying a PCB mixture in a transgenic mouse model in combination with a multivariate data reduction approach, PCBs 91, 95, 136, 149 and 174 could be excluded as substrates of multidrug resistance transporters 1a/b.

Fecal fat content

Active transport

Atropisomers

Transgenic mice

Polychlorinated biphenyls

Hotelling T2-test

Multivariate analysis

Multidrug resistance transporters

Chemometrics

Enantiomeric fraction

Principal component analysis

Details

Title: Subtitle: Assessment of the disposition of chiral polychlorinated biphenyls in female mdr 1a/b knockout versus wild-type mice using multivariate analyses
Creators: Bartłomiej Milanowski - Department of Pharmaceutical Technology, Poznań University of Medical Sciences, 6 Grunwaldzka Street, 60-780 Poznań, Poland
Janina Lulek - Department of Pharmaceutical Technology, Poznań University of Medical Sciences, 6 Grunwaldzka Street, 60-780 Poznań, Poland
Hans-Joachim Lehmler - Department of Occupational and Environmental Health, University of Iowa, College of Public Health, University of Iowa, 100 Oakdale Campus, #124 IREH, Iowa City, IA 52242-5000, United States
Izabela Kania-Korwel - Department of Occupational and Environmental Health, University of Iowa, College of Public Health, University of Iowa, 100 Oakdale Campus, #124 IREH, Iowa City, IA 52242-5000, United States
Resource Type: Journal article
Publication Details: Environment international, Vol.36(8), pp.884-892
DOI: 10.1016/j.envint.2009.10.007
PMID: 19923000
PMCID: PMC2891895
NLM abbreviation: Environ Int
ISSN: 0160-4120
eISSN: 1873-6750
Publisher: Elsevier Ltd
Language: English
Date published: 2010
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
Record Identifier: 9984000925602771

Metrics

22 Record Views

19 Times Cited - Web of Science