基于两栖动物的甲状腺干扰物测试方法分析

Analysis of Amphibian-based Assays for Thyroid Disruptors

两栖动物经历一个主要由甲状腺激素(TH)调控的变态发育过程,表现为外部形态和内部组织器官乃至TH靶基因表达的剧烈变化,这为研究和测试甲状腺干扰物提供了一个良好的模型。自2009年以来,经济合作组织(OECD)相继发布了3个基于两栖动物的甲状腺干扰物测试方法导则,即两栖动物变态试验(amphibian metamorphosis assay,AMA)导则TG 231、两栖动物幼体生长和发育试验(larval amphibian growth and development assay,LAGDA)导则TG 241和爪蛙活动胚胎甲状腺试验(X enopus eleutheroembryo thyroid assay,XETA)导则TG 248。目前这些方法已被纳入OECD的内分泌干扰物测试和评估概念框架,用于筛查测试甲状腺干扰物。不同于以自然变态发育为基础的AMA和LAGDA,国内学者发展了筛查甲状腺干扰物的T3诱导爪蛙变态试验(T3-induced Xenopus metamorphosis assay,TiXMA)。为促进对这些方法的理解和应用,本文综述了各方法的原理、终点指标、结果解释和应用现状,初步比较了各方法测试甲状腺干扰物的敏感性和特异性,并提出通过开展更多化学物质测试以对方法进行验证的必要性。

Amphibians undergo a metamorphic developmental process primarily regulated by thyroid hormone(TH),exhibiting dramatic changes in external morphology and internal tissues and organs and even in the expression of TH target genes,providing an ideal model for studying and testing thyroid disruptors.Since 2009,the O rganization for Economic Cooperation and Development(OECD)has successively released three testing guidelines for thyroid disruptors based on amphibians,namely the amphibian metamorphosis assay(AMA,TG 231),the larval amphibian growth and development assay(LAGDA,TG 241),and the Xenopus eleutheroembryo thyroid assay(XETA,TG 248).These three assays are currently incorporated into The OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupting Chemicals for screening and testing thyroid disruptors.Compared to AMA and LAGDA,which are based on spontaneous metamorphosis,Chinese researchers have developed the T 3-induced Xenopus metamorphosis assay(TiXMA)for screening thyroid disruptors.To promote the understanding and application of these assays,this paper reviews the principles,endpoints,result interpretation,and the current application status of each assay,preliminarily compares their sensitivity and specificity for thyroid disruptors.It emphasized the need to validate these assays through testing more chemicals.