T-screen and yeast assay for the detection of the thyroid-disrupting activities of cadmium, mercury, and zinc

Environ Sci Pollut Res Int. 2016 May;23(10):9843-51. doi: 10.1007/s11356-016-6095-5. Epub 2016 Feb 9.

Abstract

In the present study, a two-hybrid yeast bioassay and a T-screen were used to screen for the thyroid receptor (TR)-disrupting activity of select metallic compounds (CdCl2, ZnCl2, HgCl2, CuSO4, MnSO4, and MgSO4). The results reveal that none of the tested metallic compounds showed TR-agonistic activity, whereas ZnCl2, HgCl2, and CdCl2 demonstrated TR antagonism. For the yeast assay, the dose-response relationship of these metallic compounds was established, and the concentrations producing 20 % of the maximum effect of ZnCl2, HgCl2, and CdCl2 were 9.1 × 10(-5), 3.2 × 10(-6), and 1.2 × 10(-6) mol/L, respectively. The T-screen also supported the finding that ZnCl2, HgCl2, and CdCl2 decreased the cell proliferation at concentrations ranging from 10(-6) to 10(-4) mol/L. Furthermore, the thyroid-disrupting activity of metallic compounds in environmental water samples collected from the Guanting Reservoir, Beijing, China was evaluated. Solid-phase extraction was used to separate the organic extracts, and a modified two-hybrid yeast bioassay revealed that the metallic compounds in the water samples could affect thyroid hormone-induced signaling by decreasing the binding of the thyroid hormone. The addition of ethylenediaminetetraacetic acid (30 mg/L) could eliminate the effects. Thus, the cause(s) of the thyroid toxicity in the water samples appeared to be partly related to the metallic compounds.

Keywords: In vitro bioassay; Thyroid receptor; Thyroid-disrupting activity; Toxic metals.

MeSH terms

  • Animals
  • Beijing
  • Biological Assay / methods
  • Cadmium / toxicity
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Edetic Acid / chemistry
  • Endocrine Disruptors / toxicity*
  • Humans
  • Mercury / toxicity
  • Metals, Heavy / toxicity*
  • Rats
  • Receptors, Thyroid Hormone* / agonists
  • Receptors, Thyroid Hormone* / antagonists & inhibitors
  • Thyroid Gland / drug effects*
  • Thyroid Gland / metabolism
  • Thyroid Hormones / metabolism
  • Two-Hybrid System Techniques
  • Water Pollutants, Chemical / toxicity*
  • Yeasts / drug effects*
  • Yeasts / genetics
  • Yeasts / metabolism
  • Zinc / toxicity

Substances

  • Endocrine Disruptors
  • Metals, Heavy
  • Receptors, Thyroid Hormone
  • Thyroid Hormones
  • Water Pollutants, Chemical
  • Cadmium
  • Edetic Acid
  • Mercury
  • Zinc