Study on the development of bioassay system for organic halogenated compounds with thyroid-disrupting activity

甲状腺干扰有机卤化物生物测定体系的建立研究

基本信息

批准号：
16310038
负责人：
YAMAUCHI Kiyoshi
金额：
$ 7.58万
依托单位：
Shizuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16310038/
关键词：
environmental pollutants thyroid hormone endocrine disruption bioassay 環境ホルモン受容体

项目摘要

In vertebrates, thyroid hormones are essential for post-embryonic development, such as establishing the central nervous system in mammals and metamorphosis in amphibians. The present study focused on the extra-thyroidal processes that environmental chemicals are known to or suspected to target in the thyroid hormone-signaling pathway. We developed three in vitro and one in vivo bioassays, which detect chemicals interfering with thyroid hormone binding to plasma transthyretin (TTR assay), thyroid hormone binding to nuclear receptor (TR assay), induction of thyroid hormone-dependent reporter gene expression (Luc assay, and gene expression during thyroid hormone-induced amphibian metamorphosis (metamorphosis assay). Several organohalogens affect different aspects of the extra-thyroidal thyroid-hormone-signaling pathway but hardly affect thyroid hormone binding to receptors. Amphibian tadpoles are most sensitive to the effects of environmental chemicals during specific thyroid-hormone-related developmental windows. The thyroid hormone-disrupting activity of contaminants in aquatic environments in Japan and Thailand was surveyed by these bioassays. Our assays demonstrated that wastewater treatment effectively removed the TH-disrupting contaminants from wastewater in paper manufacturing plants and sewage-treatment plants. The Luc assay indicated that sewage-treatment plant effluents in Japan contained Ta-like activity whereas that in Thailand contained anti-Ta-like activity. It is likely that the three in vitro bioassays detected the same or different contaminants with TH-disrupting activity in a water sample-dependent manner. Our results indicate that a combination of several in vitro bioassays facilitates the rapid screening of environmental water samples to identify the locations of contaminants with TH-disrupting activity.

在脊椎动物中，甲状腺激素对于胚胎后发育至关重要，例如在两栖动物中建立中枢神经系统和变形。本研究的重点是已知或怀疑在甲状腺激素信号途径中靶向的甲状腺外过程。我们开发了三个体外和1个体内生物测定，它们检测到与血浆转换蛋白（TTR分析）结合甲状腺激素的化学物质，甲状腺激素与核受体的结合（TR分析），甲状腺激素依赖甲状腺依赖性的报告基因表达（Lucnodectement Gene sissay），甲状腺激素诱导的两栖动物变态（变态测定）的基因表达会影响甲状腺外甲状腺激素信号的不同方面。特定的甲状腺激素相关发育窗口中的环境化学物质在日本和泰国的水生环境中污染物的污染物中断活性。制造厂和污水处理厂。 LUC测定法表明，日本的污水处理厂废水具有类似TA的活性，而在泰国中，污水处理厂具有反-TA样活性。这三个体外生物测定可能以水样依赖性方式检测到具有Th distruption活性的相同或不同的污染物。我们的结果表明，几种体外生物测定的结合促进了对环境水样品的快速筛选，以鉴定具有Th Distruption活性的污染物的位置。