Pure non-dioxin-like PCB congeners suppress induction of AhR-dependent endpoints in rat liver cells
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26077315
DOI
10.1007/s11356-015-4819-6
PII: 10.1007/s11356-015-4819-6
Knihovny.cz E-resources
- Keywords
- Aryl hydrocarbon receptor, Cytochrome P450, DR-CALUX® assay, Disruption of contact inhibition, NDL-PCBs, Relative effect potency,
- MeSH
- Cell Line MeSH
- Cytochrome P-450 CYP1A1 genetics metabolism MeSH
- Epithelial Cells cytology drug effects metabolism MeSH
- Gene Expression drug effects MeSH
- Hepatocytes cytology drug effects metabolism MeSH
- Liver drug effects metabolism MeSH
- Rats MeSH
- Polychlorinated Biphenyls chemistry toxicity MeSH
- Cell Proliferation drug effects MeSH
- Receptors, Aryl Hydrocarbon genetics metabolism MeSH
- Signal Transduction drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cytochrome P-450 CYP1A1 MeSH
- Polychlorinated Biphenyls MeSH
- Receptors, Aryl Hydrocarbon MeSH
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 μM), 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.
Department of Chemistry Umeå University SE 901 87 Umeå Sweden
Institute for Environmental Studies VU University Amsterdam 1081 HV Amsterdam The Netherlands
See more in PubMed
Toxicol Lett. 2010 Apr 15;194(1-2):26-33 PubMed
Oncogene. 2008 Apr 3;27(15):2198-207 PubMed
Exp Cell Res. 1984 Sep;154(1):38-52 PubMed
Chem Res Toxicol. 2006 Jan;19(1):92-101 PubMed
J Biol Chem. 2010 Nov 12;285(46):35599-605 PubMed
Methods. 2001 Dec;25(4):402-8 PubMed
Toxicol Sci. 2006 Jul;92(1):157-73 PubMed
Chemosphere. 2011 Nov;85(9):1423-9 PubMed
Natl Toxicol Program Tech Rep Ser. 2006 May;(529):4-168 PubMed
Mol Pharmacol. 2010 Oct;78(4):608-16 PubMed
Toxicol Sci. 2011 May;121(1):88-100 PubMed
Toxicol Sci. 2011 May;121(1):123-31 PubMed
Mol Cancer Res. 2006 Mar;4(3):135-50 PubMed
Natl Toxicol Program Tech Rep Ser. 2006 Aug;(530):1-258 PubMed
Teratog Carcinog Mutagen. 1997-1998;17 (4-5):285-304 PubMed
J Hepatol. 2002 Apr;36(4):552-64 PubMed
Toxicol Sci. 2006 Oct;93(2):223-41 PubMed
Environ Int. 2003 Sep;29(6):861-77 PubMed
Chem Biol Interact. 1981 Apr;35(1):1-12 PubMed
Eur J Biochem. 2000 Sep;267(17):5421-6 PubMed
Mutat Res. 2006 Apr 11;596(1-2):43-56 PubMed
Pharmacol Ther. 1995;67(2):247-81 PubMed
J Pharm Sci. 1990 Jul;79(7):592-4 PubMed
Toxicol Appl Pharmacol. 2002 Sep 1;183(2):117-26 PubMed
Toxicol Sci. 2005 Jan;83(1):53-63 PubMed
Toxicol Appl Pharmacol. 1996 Apr;137(2):316-25 PubMed
J Biochem Mol Toxicol. 2000;14 (2):73-81 PubMed
Environ Toxicol. 2004 Oct;19(5):480-9 PubMed
