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首页> 外文期刊>Environmental Science & Technology >Gene Expression Profiling for Understanding Chemical Causation of Biological Effects for Complex Mixtures: A Case Study on Estrogens
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Gene Expression Profiling for Understanding Chemical Causation of Biological Effects for Complex Mixtures: A Case Study on Estrogens

机译：基因表达谱分析理解复杂混合物生物学效应的化学成因：雌激素的案例研究

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Gene expression profiling offers considerable potential for identifying chemical causation of effects induced in exposures to complex mixtures, and for understanding the mechanistic basis for their phenotypic effects. We characterized gene expression responses in livers and gonads of fathead minnow (Pimephales promelas) exposed (for 14-21 days)to estrogenic wastewater treatment works final effluents with varying potencies and assessed the extent to which these expression profiles mapped with those induced by individual steroid estrogens present in the effluents (17β-estradiol and 17α-ethinylestradiol) and, thus, were diagnostic of estrogen exposure. For these studies, we adopted a targeted approach (via real-time PCR) with a suite of 12 genes in liver and 21 genes in gonad known to play key roles in reproduction, growth and development (processes controlled by estrogens) and responses were compared with effects on phenotypic end points indicative of feminization. Gene responses to effluent were induced predominantly in a linear (monotonic) concentration-dependent manner but were complex with many genes responding differently between tissue types and sexes. The gene expression profiles for the estrogenic effluents and the individual steroid estrogens had many common features. There were marked differences in the profiles between the two effluents, however, that were not explained by differences in their estrogenic potencies, suggesting that these may have arisen as a consequence of differences in the contents of other chemicals, which may act directly or indirectly with the estrogen-response pathway to alter estrogen-induced gene expression. These data demonstrate that the patterns of gene expression induced by estrogenic effluents, although complex, can be diagnostic for some of the estrogens they contain and provide insights into the mechanistic basis for the phenotypic effects seen.
机译：基因表达谱分析为鉴定因暴露于复杂混合物中引起的效应的化学成因以及了解其表型效应的机理基础提供了巨大的潜力。我们对暴露于雌激素废水处理（14-21天）的黑头min鱼（Pimephales promelas）的肝脏和性腺中的基因表达响应进行了表征，并以不同的效价处理了最终出水，并评估了这些表达谱与单个类固醇诱导的表达谱之间的对应程度流出物中存在的雌激素（17β-雌二醇和17α-乙炔基雌二醇）因此可以诊断出雌激素暴露。对于这些研究，我们采用了针对性的方法（通过实时PCR），将肝脏中的12个基因和性腺中的21个基因组成一组，这些基因在生殖，生长和发育（雌激素控制的过程）中起着关键作用，并比较了反应对指示女性化的表型终点有影响。对污水的基因反应主要以线性（单调）浓度依赖性方式诱导，但是与许多基因复杂，组织类型和性别之间的反应不同。雌激素流出物和单个类固醇雌激素的基因表达谱具有许多共同特征。两种流出物之间的轮廓存在显着差异，但不能通过其雌激素效价的差异来解释，这表明这些可能是由于其他化学物质含量不同而引起的，这些化学物质可能直接或间接地与雌激素反应途径来改变雌激素诱导的基因表达。这些数据表明，由雌激素流出物诱导的基因表达模式虽然复杂，但可以诊断出它们所含的某些雌激素，并为所见表型效应的机理基础提供了见识。

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