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Environmental health perspectives
Feb, 2004;112 (2): 163-9.

Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR).

Michelle M Tabb, Vladyslav Kholodovych, Felix Grün, Changcheng Zhou, William J Welsh, Bruce Blumberg
Author Information
  1. Michelle M Tabb: Department of Developmental and Cell Biology, University of California, Irvine, California 92697-2300, USA.
PMID: 14754570 DOI: 10.1289/ehp.6560

Abstract

Polychlorinated biphenyls (PCBs) are a family of persistent organic contaminants suspected to cause adverse effects in wildlife and humans. In rodents, PCBs bind to the aryl hydrocarbon (AhR) and pregnane X receptors (PXR) inducing the expression of catabolic cytochrome p450 enzymes of the CYP1A and 3A families. We found that certain highly chlorinated PCBs are potent activators of rodent PXR but antagonize its human ortholog, the steroid and xenobiotic receptor (SXR), inhibiting target gene induction. Thus, exposure to PCBs may blunt the human xenobiotic response, inhibiting the detoxification of steroids, bioactive dietary compounds, and xenobiotics normally mediated by SXR. The antagonistic PCBs are among the most stable and abundant in human tissues. These findings have important implications for understanding the biologic effects of PCB exposure and the use of animal models to predict the attendant risk.

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Grants

  1. CA-87222/NCI NIH HHS
  2. N01-DK-92310/NIDDK NIH HHS
  3. T32 HD-07029/NICHD NIH HHS

MeSH Term

Animals
Cell Culture Techniques
Diet
Environmental Pollutants
Humans
Inactivation, Metabolic
Mice
Polychlorinated Biphenyls
Pregnane X Receptor
Rats
Receptors, Steroid
Risk Assessment
Steroids
Xenobiotics

Chemicals

Environmental Pollutants
Pregnane X Receptor
Receptors, Steroid
Steroids
Xenobiotics
Polychlorinated Biphenyls
Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.
Article has an altmetric score of 3

Word Cloud

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