Competitive interactions of chlorinated phenol compounds with 3,3′,5-triiodothyronine binding to transthyretin:: detection of possible thyroid-disrupting chemicals in environmental waste water

Chlorinated phenol compounds, such as the chlorinated derivatives of bisphenol A, have been detected in effluents from paper manufacturing plants. We investigated the effects of bisphenol A, nonylphenol, and their seven chlorinated derivatives on 3,3',5[I-125]triiodothyronine ([I-125]T-3) binding to purified chicken and bullfrog transthyretin (cTTR and bTTR) and to the ligand-binding domains of chicken and bullfrog thyroid hormone receptor beta (cTR LBD) Lind bTR LBD). The concentrations at which the chlorinated derivatives displaced [I-125]T-3 from TTR were 10-10(3) times less than those of their parent molecules. 2,6- Dichloro-4-nonylphenol and 3,3',5-trichlorobisphenol A were the most potent competitors of T-3 binding to cTTR and to bTTR, respectively. The interactions of the chlorinated derivatives with the cTR and the bTR LBDs were weaker than those of the chlorinated derivatives with cTTR and bTTR. Chlorinated derivatives with a greater degree of chlorination were more efficient competitors of T-3 binding to TTR and TR. A structure-activity relationship between the phenol compounds and TTR (TTR assay) and TR (TR assay) was established. Structures with chlorine in either ortho position or both ortho positions, with respect to the hydroxy group, were more efficient competitors. Chemicals that interacted with bTTR, cTTR, and Japanese quail TTR were detected in water downstream of effluents from paper manufacturing plants using the TTR assay. As some of the chlorinated bisphenols and nonylphenols were potent competitors of T-3 binding to TTRs, the TTR assay could be applied as primary screening for possible thyroid-disrupting chemicals in environmental waste water. (C) 2003 Elsevier Science (USA). All rights reserved.