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Reprod Toxicol ; 96: 432-444, 2020 09.
Article in English | MEDLINE | ID: mdl-31077750

ABSTRACT

We developed a thyroid testing panel to assess endocrine disrupting chemicals (EDCs) capacities to bind either the thyroid receptor ß (TRß) or the thyroid hormones transporter transthyretin (TTR). We first stably transfected a human U2OS cell line with TRß and a luciferase reporter construct to develop the TRß CALUX® reporter gene assay to assess chemicals' potential to interact with TRß. Secondly, we combined a TTR-binding assay with the TRß CALUX (TTR-TRß CALUX) and optimized the system to evaluate the competitive properties of EDCs towards T4 for TTR binding. Both systems were evaluated with a range of known thyroid-disrupting compounds. The agonistic/antagonistic TRß CALUX successfully predicted 9/9 and 9/12 test compounds, respectively. The TTR-TRß CALUX predicted 9/9 compounds and demonstrated competitive activities when analyzing waste water samples. We concluded that the proposed test battery is a promising screening method able to efficiently generate data on thyroid hormone interferences by chemicals.


Subject(s)
Biological Assay , Endocrine Disruptors/pharmacology , Prealbumin/metabolism , Thyroid Hormone Receptors beta/metabolism , Thyroid Hormones/metabolism , Binding, Competitive , Cell Line , Genes, Reporter , Humans , Luciferases/genetics , Prealbumin/genetics , Thyroid Hormone Receptors beta/agonists , Thyroid Hormone Receptors beta/antagonists & inhibitors , Thyroid Hormone Receptors beta/genetics
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