Biosensor discovery of thyroxine transport disrupting chemicals
- RIKILT-Institute of Food Safety, Wageningen UR, P.O. Box 230, 6700 AE Wageningen (Netherlands)
- ELTI Support-VOF, Drieskensacker 12-10, 6546 MH Nijmegen (Netherlands)
- Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)
- Vrije Universiteit Amsterdam, Division of Chemistry, Department of Analytical Chemistry and Applied Spectroscopy, de Boelelaan 1083, 1081 HV Amsterdam (Netherlands)
- Wageningen University, Toxicology Section, 6703 HE Wageningen (Netherlands)
Ubiquitous chemicals may interfere with the thyroid system that is essential in the development and physiology of vertebrates. We applied a surface plasmon resonance (SPR) biosensor-based screening method for the fast screening of chemicals with thyroxine (T4) transport disrupting activity. Two inhibition assays using the main thyroid hormone transport proteins, T4 binding globulin (TBG) and transthyretin (TTR), in combination with a T4-coated biosensor chip were optimized and automated for screening chemical libraries. The transport protein-based biosensor assays were rapid, high throughput and bioeffect-related. A library of 62 chemicals including the natural hormones, polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs) and metabolites, halogenated bisphenol A (BPA), halogenated phenols, pharmaceuticals, pesticides and other potential environmentally relevant chemicals was tested with the two assays. We discovered ten new active compounds with moderate to high affinity for TBG with the TBG assay. Strikingly, the most potent binding was observed with hydroxylated metabolites of the brominated diphenyl ethers (BDEs) BDE 47, BDE 49 and BDE 99, that are commonly found in human plasma. The TTR assay confirmed the activity of previously identified hydroxylated metabolites of PCBs and PBDEs, halogenated BPA and genistein. These results show that the hydroxylated metabolites of the ubiquitous PBDEs not only target the T4 transport at the TTR level, but also, and to a great extent, at the TBG level where most of the T4 in humans is circulating. The optimized SPR biosensor-based transport protein assay is a suitable method for high throughput screening of large libraries for potential thyroid hormone disrupting compounds.
- OSTI ID:
- 21144131
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 232, Issue 1; Other Information: DOI: 10.1016/j.taap.2008.06.014; PII: S0041-008X(08)00269-X; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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