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Evaluation of tetrabromobisphenol A effects on human glucocorticoid and androgen receptors: A comparison of results from human- with yeast-based in vitro assays

Beck, Katharina R. and Sommer, Tanja J. and Schuster, Daniela and Odermatt, Alex. (2016) Evaluation of tetrabromobisphenol A effects on human glucocorticoid and androgen receptors: A comparison of results from human- with yeast-based in vitro assays. Toxicology, 370. pp. 70-77.

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Official URL: http://edoc.unibas.ch/52892/

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Abstract

The incidence of immune-related diseases increased over the last years in industrialized countries, suggesting a contribution of environmental factors. Impaired glucocorticoid action has been associated with immune disorders. Thus, there is an increasing interest to identify chemicals disrupting glucocorticoid action. The widely used flame retardant tetrabromobisphenol A (TBBPA) was reported earlier to potently inhibit glucocorticoid receptor (GR) and moderately androgen receptor (AR) activity in yeast-based reporter gene assays. To further characterize possible GR disrupting effects of TBBPA, transactivation experiments using a human HEK-293 cell-based reporter gene assay and cell-free receptor binding experiments were performed in the present study. Both, transactivation and GR binding experiments failed to detect any activity of TBBPA on GR function. Molecular docking calculations supported this observation. Additionally, the current study could confirm the antiandrogenic activity of TBBPA seen in the yeast assay, although the effect was an order of magnitude less pronounced in the HEK-293 cell-based system. In conclusion, TBBPA does not directly affect GR function and, considering its rapid metabolism and low concentrations found in humans, it is unlikely to cause adverse effects by acting through AR. This study emphasizes the use of cell-free assays in combination with cell-based assays for the in vitro evaluation of endocrine disrupting chemicals.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
UniBasel Contributors:Beck, Katharina and Sommer, Tanja and Odermatt, Alex
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0300-483X
e-ISSN:1879-3185
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:26 Oct 2017 14:55
Deposited On:26 Oct 2017 14:55

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