Crump Doug, Werry Kate, Veldhoen Nik, Van Aggelen Graham, Helbing Caren C
Department of Biochemistry and Microbiology, University of Victoria, British Columbia, Canada.
Environ Health Perspect. 2002 Dec;110(12):1199-205. doi: 10.1289/ehp.021101199.
A growing number of substances released into the environment disrupt normal endocrine mechanisms in a wide range of vertebrates. Little is known about the effects and identities of endocrine-disrupting chemicals (EDCs) that target thyroid hormone (TH) action, particularly at the cellular level. Frog tadpole metamorphosis depends completely on TH, which has led to the suggestion of a metamorphosis-based assay for screening potential EDCs. A major mechanism of TH action is the alteration of gene expression via hormone-bound nuclear receptors. To assess the gene expression profiles in the frog model, we designed a novel multispecies frog cDNA microarray. Recently, the preemergent herbicide acetochlor was shown to accelerate 3,5,3 -triiodothyronine (T3)-induced forelimb emergence and increase mRNA expression of thyroid hormone ss receptors in ranid tadpoles. Here we show that T3-induced metamorphosis of Xenopus laevis, a species commonly used in the laboratory, is accelerated upon acute exposure to an environmentally relevant level of acetochlor. The morphologic changes observed are preceded by alterations in gene expression profiles detected in the tadpole tail, and the nature of these profiles suggest a novel mechanism of action for acetochlor.
越来越多释放到环境中的物质会干扰多种脊椎动物的正常内分泌机制。对于针对甲状腺激素（TH）作用的内分泌干扰化学物质（EDC）的影响和特性，人们了解甚少，尤其是在细胞水平上。青蛙蝌蚪的变态完全依赖于TH，这引发了一种基于变态的检测方法来筛选潜在EDC的建议。TH作用的一个主要机制是通过激素结合的核受体改变基因表达。为了评估青蛙模型中的基因表达谱，我们设计了一种新型的多物种青蛙cDNA微阵列。最近，已证明芽前除草剂乙草胺能加速3,5,3'-三碘甲状腺原氨酸（T3）诱导的前肢出现，并增加蛙科蝌蚪中甲状腺激素β受体的mRNA表达。在此我们表明，实验室常用的非洲爪蟾在急性暴露于环境相关水平的乙草胺后，T3诱导的变态会加速。观察到的形态变化之前，蝌蚪尾巴中检测到的基因表达谱会发生改变，这些谱的性质表明乙草胺有一种新的作用机制。
