Yamauchi Kiyoshi, Ishihara Akinori, Fukazawa Hitoshi, Terao Yoshiyasu
Department of Biology and Geoscience, Faculty of Science, Shizuoka University, Shizuoka, Japan.
Toxicol Appl Pharmacol. 2003 Mar 1;187(2):110-7. doi: 10.1016/s0041-008x(02)00045-5.
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-[(125)I]triiodothyronine ([(125)I]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 and bTR LBD). The concentrations at which the chlorinated derivatives displaced [(125)I]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.
在造纸厂排放的废水中已检测到氯化酚类化合物，如双酚A的氯化衍生物。我们研究了双酚A、壬基酚及其七种氯化衍生物对3,3',5-[(125)I]三碘甲状腺原氨酸([(125)I]T(3))与纯化的鸡和牛蛙转甲状腺素蛋白（cTTR和bTTR）以及鸡和牛蛙甲状腺激素受体β的配体结合域（cTR LBD和bTR LBD）结合的影响。氯化衍生物从TTR上取代[(125)I]T(3)的浓度比其母体分子低10 - 10(3)倍。2,6-二氯-4-壬基酚和3,3',5-三氯双酚A分别是T(3)与cTTR和bTTR结合的最有效竞争者。氯化衍生物与cTR和bTR LBD的相互作用比与cTTR和bTTR的相互作用弱。氯化程度更高的氯化衍生物是T(3)与TTR和TR结合的更有效竞争者。建立了酚类化合物与TTR（TTR测定）和TR（TR测定）之间的构效关系。相对于羟基，在邻位或两个邻位带有氯的结构是更有效的竞争者。使用TTR测定法在造纸厂废水下游的水中检测到了与bTTR、cTTR和日本鹌鹑TTR相互作用的化学物质。由于一些氯化双酚和壬基酚是T(3)与TTR结合的有效竞争者，TTR测定法可作为对环境废水中可能的甲状腺干扰化学物质进行初步筛选的方法。
