Gene Expression Profiles for Detecting and Distinguishing Potential Endocrine-Disrupting Compounds in Environmental Samples

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• 作者：Dong-Yu Wang ; Bruce McKague ; Steven N. Liss ; and Elizabeth A. Edwards
• 刊名：Environmental Science & Technology
• 出版年：2004
• 出版时间：December 1, 2004
• 年：2004
• 卷：38
• 期：23
• 页码：6396 - 6406
• 全文大小：943K
• 年卷期：v.38,no.23(December 1, 2004)
• ISSN：1520-5851

文摘

Industrial and municipal processes may produce andrelease endocrine-disrupting compounds (EDCs) into theenvironment, but the exact nature of their effects is difficultto investigate. EDCs typically exert their effect by affectinggene expression aberrantly. To determine if geneexpression profiles could be used to detect and distinguishestrogenic EDCs, an estrogen receptor positive humanbreast cancer cell line (MCF-7) was exposed to knownestrogenic compounds, suspected EDCs, and extracts fromthree effluent samples. A set of specifically estrogen-regulated genes was identified by microarray analysis. Nineestrogen up-regulated genes (IGFBP4, HSPA8, B4GALT1,XBP1, KRT8, GTPBP4, HNRPAB, SLC2A1, and CALM1) andtwo estrogen down-regulated genes (ID2 and ZNF217)were consistently detectable in response to estrogen andother estrogenic compounds. Gene expression patternsin cells that were exposed to effluent sample extracts werecompared to gene expression patterns in cells that wereexposed to known endocrines. Using this technique,two of the effluent samples were shown to have estrogenicactivity. This approach could easily be extended toscreen for other types of receptor-mediated endocrinedisruption. For example, cells expressing androgen or arylhydrocarbon receptors could be used in gene expressionprofiling assays to detect androgenic effects or for thepresence of bioactive aromatic hydrocarbons. Geneexpression profiling is emerging as a sensitive and specificmethod to screen complex samples for endocrinedisrupting activity.