Journal article
In vitro profiling of toxic effects of prominent environmental lower-chlorinated PCB congeners linked with endocrine disruption and tumor promotion
Environmental pollution (1987), Vol.237, pp.473-486
06/2018
DOI: 10.1016/j.envpol.2018.02.067
PMCID: PMC5908724
PMID: 29518658
Abstract
The mechanisms contributing to toxic effects of airborne lower-chlorinated PCB congeners (LC-PCBs) remain poorly characterized. We evaluated in vitro toxicities of environmental LC-PCBs found in both indoor and outdoor air (PCB 4, 8, 11, 18, 28 and 31), and selected hydroxylated metabolites of PCB 8, 11 and 18, using reporter gene assays, as well as other functional cellular bioassays. We focused on processes linked with endocrine disruption, tumor promotion and/or regulation of transcription factors controlling metabolism of both endogenous compounds and xenobiotics. The tested LC-PCBs were found to be mostly efficient anti-androgenic (within nanomolar – micromolar range) and estrogenic (at micromolar concentrations) compounds, as well as inhibitors of gap junctional intercellular communication (GJIC) at micromolar concentrations. PCB 8, 28 and 31 were found to partially inhibit the aryl hydrocarbon receptor (AhR)-mediated activity. The tested LC-PCBs were also partial constitutive androstane receptor (CAR) and pregnane X receptor (PXR) agonists, with PCB 4, 8 and 18 being the most active compounds. They were inactive towards other nuclear receptors, such as vitamin D receptor, thyroid receptor α, glucocorticoid receptor or peroxisome proliferator-activated receptor γ. We found that only PCB 8 contributed to generation of oxidative stress, while all tested LC-PCBs induced arachidonic acid release (albeit without further modulations of arachidonic acid metabolism) in human lung epithelial cells. Importantly, estrogenic effects of hydroxylated (OH-PCB) metabolites of LC-PCBs (4-OH-PCB 8, 4-OH-PCB 11 and 4′-OH-PCB 18) were higher than those of the parent PCBs, while their other toxic effects were only slightly altered or suppressed. This suggested that metabolism may alter toxicity profiles of LC-PCBs in a receptor-specific manner. In summary, anti-androgenic and estrogenic activities, acute inhibition of GJIC and suppression of the AhR-mediated activity were found to be the most relevant modes of action of airborne LC-PCBs, although they partially affected also additional cellular targets.
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•In vitro toxicities of environmental LC-PCBs and hydroxylated LC-PCBs were estimated.•LC-PCBs induced anti-androgenic and estrogenic effects, inhibition of AhR signaling and moderate CAR/PXR-mediated activities.•LC-PCBs were found to inhibit gap junctional intercellular communication and induce AA release.•Hydroxylation of LC-PCBs altered their toxicities in a receptor-specific manner, promoting their estrogenic effects.
In vitro screening provides novel information about toxic modes of action of lower chlorinated PCBs and their metabolites, related to endocrine disruption and tumor promotion.
Details
- Title: Subtitle
- In vitro profiling of toxic effects of prominent environmental lower-chlorinated PCB congeners linked with endocrine disruption and tumor promotion
- Creators
- Kateřina Pěnčíková - Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech RepublicLucie Svržková - Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech RepublicSimona Strapáčová - Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech RepublicJiří Neča - Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech RepublicIveta Bartoňková - Department of Cell Biology and Genetics, Faculty of Science, Šlechtitelů 11, Palacký University, 78371 Olomouc, Czech RepublicZdeněk Dvořák - Department of Cell Biology and Genetics, Faculty of Science, Šlechtitelů 11, Palacký University, 78371 Olomouc, Czech RepublicMartina Hýžďalová - Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech RepublicJakub Pivnička - Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech RepublicLenka Pálková - Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech RepublicHans-Joachim Lehmler - Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, 52242, IA, USAXueshu Li - Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, 52242, IA, USAJan Vondráček - Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech RepublicMiroslav Machala - Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech Republic
- Resource Type
- Journal article
- Publication Details
- Environmental pollution (1987), Vol.237, pp.473-486
- DOI
- 10.1016/j.envpol.2018.02.067
- PMID
- 29518658
- PMCID
- PMC5908724
- NLM abbreviation
- Environ Pollut
- ISSN
- 0269-7491
- eISSN
- 1873-6424
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/501100001824, name: Czech Science Foundation, award: P503/12/G147, 16-17085S; DOI: 10.13039/501100004240, name: Czech Academy of Sciences; DOI: 10.13039/501100007059, name: Palacký University in Olomouc; name: Czech Ministry of Agriculture, award: RO 0517
- Language
- English
- Date published
- 06/2018
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
- Record Identifier
- 9984065483002771
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