| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Kamstra, Jorke H. Strapácová, Simona Andersson, Patrik L. Hamers, Timo Machala, Miroslav Vondrácek, Jan Brenerová, Petra |
| Description |
Country affiliation: Czech Republic Author Affiliation: Brenerová P ( Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100, Brno, Czech Republic.); Hamers T ( Institute for Environmental Studies, VU University Amsterdam, 1081 HV, Amsterdam, The Netherlands.); Kamstra JH ( Institute for Environmental Studies, VU University Amsterdam, 1081 HV, Amsterdam, The Netherlands.); Vondrácek J ( Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, 62165, Brno, Czech Republic.); Strapácová S ( Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100, Brno, Czech Republic.); Andersson PL ( Department of Chemistry, Umeå University, SE-901 87, Umeå, Sweden.); Machala M ( Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100, Brno, Czech Republic. machala@vri.cz.) |
| Abstract |
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. |
| ISSN |
09441344 |
| Issue Number |
3 |
| Volume Number |
23 |
| e-ISSN |
16147499 |
| Journal |
Environmental Science and Pollution Research |
| Language |
English |
| Publisher |
Springer |
| Publisher Date |
2016-02-01 |
| Publisher Place |
Germany |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Liver Drug Effects Polychlorinated Biphenyls Chemistry Toxicity Receptors, Aryl Hydrocarbon Metabolism Animals Cell Line Cell Proliferation Cytochrome P-450 Cyp1a1 Genetics Epithelial Cells Cytology Gene Expression Hepatocytes Rats Signal Transduction Journal Article Research Support, Non-u.s. Gov't Discipline Environmental Science Discipline Environmental Chemistry |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Environmental Chemistry Health, Toxicology and Mutagenesis Pollution Medicine |
