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Pure non-dioxin-like PCB congeners suppress induction of AhR-dependent endpoints in rat liver cells
Department of Chemistry and Toxicology, Veterinary Research Institute.
Institute for Environmental Studies, VU University Amsterdam.
Institute for Environmental Studies, VU University Amsterdam.
Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic.
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2016 (English)In: Environmental science and pollution research international, ISSN 0944-1344, E-ISSN 1614-7499, Vol. 23, no 3, 2099-2107 p.Article in journal (Refereed) PublishedText
Abstract [en]

The relative potencies of non-ortho-substituted coplanar polychlorinated biphenyl (PCB) congeners to activate the aryl hydrocarbon receptor (AhR) and to cause the AhR-dependent toxic events are essential for their risk assessment. Since some studies suggested that abundant non-dioxin-like PCB congeners (NDL-PCBs) may alter the AhR activation by PCB mixtures and possibly cause non-additive effects, we evaluated potential suppressive effects of NDL-PCBs on AhR activation, using a series of 24 highly purified NDL-PCBs. We investigated their impact on the model AhR agonist-induced luciferase reporter gene expression in rat hepatoma cells and on induction of CYP1A1/1B1 mRNAs and deregulation of AhR-dependent cell proliferation in rat liver epithelial cells. PCBs 128, 138, and 170 significantly suppressed AhR activation (with IC50 values from 1.4 to 5.6 mu M), followed by PCBs 28, 47, 52, and 180; additionally, PCBs 122, 153, and 168 showed low but still significant potency to reduce luciferase activity. Detection of CYP1A1 mRNA levels in liver epithelial cells largely confirmed these results for the most abundant NDL-PCBs, whereas the other AhR-dependent events (CYP1B1 mRNA expression, induction of cell proliferation in confluent cells) were less sensitive to NDL-PCBs, thus indicating a more complex regulation of these endpoints. The present data suggest that some NDL-PCBs could modulate overall dioxin-like effects in complex mixtures.

Place, publisher, year, edition, pages
Springer, 2016. Vol. 23, no 3, 2099-2107 p.
Keyword [en]
NDL-PCBs, Aryl hydrocarbon receptor, DR-CALUX (R) assay, Cytochrome P450, Disruption of contact hibition, Relative effect potency
National Category
Environmental Sciences
URN: urn:nbn:se:umu:diva-116733DOI: 10.1007/s11356-015-4819-6ISI: 000368376800014PubMedID: 26077315OAI: diva2:904838
Available from: 2016-02-19 Created: 2016-02-11 Last updated: 2016-02-23Bibliographically approved

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