Journal
ENVIRONMENTAL HEALTH PERSPECTIVES
Volume 112, Issue 2, Pages 163-169Publisher
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.6560
Keywords
metabolism; polychlorinated biphenyls; PXR; SXR; xenobiotic
Funding
- NCI NIH HHS [CA-87222] Funding Source: Medline
- NICHD NIH HHS [T32 HD-07029] Funding Source: Medline
- NIDDK NIH HHS [N01-DK-92310] Funding Source: Medline
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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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