BACKGROUND An individual's response to environmental exposures varies depending on their genotype, which has been termed the gene-environment interaction. The phenotype of cell exposed can also be a key determinant in the response to physiological cues, indicating that a cell-gene-environment interaction may exist. We investigated whether the cellular environment could alter the transcriptional response to environmental chemicals. Publicly available gene expression array data permitted a targeted comparison of the transcriptional response to a unique subclass of environmental chemicals that alter the activity of the estrogen receptor, xenoestrogens. RESULTS Thirty xenoestrogens were included in the analysis, for which 426 human gene expression studies were identified. Comparisons were made for studies that met the predefined criteria for exposure length, concentration, and experimental replicates. The cellular response to the phytoestrogen genistein resulted in remarkably unique transcriptional profiles in breast, liver, and uterine cell-types. Analysis of gene regulatory networks and molecular pathways revealed that the cellular context mediated the activation or repression of functions important to cellular organization and survival, including opposing effects by genistein in breast vs. liver and uterine cell-types. When controlling for cell-type, xenoestrogens regulate unique gene networks and biological functions, despite belonging to the same class of environmental chemicals. Interestingly, the genetic sex of the cell-type also strongly influenced the transcriptional response to xenoestrogens in the liver, with only 22% of the genes significantly regulated by genistein common between male and female cells. CONCLUSIONS Our results demonstrate that the transcriptional response to environmental chemicals depends on a variety of factors, including the cellular context, the genetic sex of a cell, and the individual chemical. These findings highlight the importance of evaluating the impact of exposure across cell-types, as the effect is responsive to the cellular environment. These comparative genetic results support the concept of a cell-gene-environment interaction.

中文翻译：

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基因X环境：细胞环境控制着对环境化学物质的转录反应。

背景技术个体对环境暴露的反应根据其基因型而变化，该基因型被称为基因-环境相互作用。暴露细胞的表型也可能是对生理线索反应的关键决定因素，表明可能存在细胞-基因-环境相互作用。我们调查了细胞环境是否可以改变对环境化学物质的转录反应。公开可用的基因表达阵列数据允许针对转录反应与改变雌激素受体异种雌激素活性的独特的环境化学亚类进行靶向比较。结果分析中包括三十种异雌激素，共鉴定了426个人类基因表达研究。对符合暴露长度，浓度和实验重复的预定标准的研究进行比较。细胞对植物雌激素染料木黄酮的反应导致乳腺癌，肝癌和子宫细胞类型的转录谱非常独特。对基因调节网络和分子途径的分析表明，细胞环境介导了对细胞组织和存活重要的功能的激活或抑制，包括金雀异黄素在乳腺，肝脏和子宫细胞类型中的相反作用。当控制细胞类型时，异雌激素调节独特的基因网络和生物学功能，尽管属于同一类环境化学品。有趣的是，细胞类型的遗传性别也强烈影响了肝脏中对异雌激素的转录反应，仅有22％的基因受染料木素在雄性和雌性细胞之间共有的显着调控。结论我们的结果表明，对环境化学物质的转录反应取决于多种因素，包括细胞环境，细胞的遗传性别和单个化学物质。这些发现凸显了评估暴露于各种细胞类型的影响的重要性，因为这种影响是对细胞环境的响应。这些比较的遗传结果支持细胞-基因-环境相互作用的概念。和个别化学品。这些发现凸显了评估暴露于各种细胞类型的影响的重要性，因为这种影响是对细胞环境的响应。这些比较的遗传结果支持细胞-基因-环境相互作用的概念。和个别化学品。这些发现凸显了评估暴露于各种细胞类型的影响的重要性，因为这种影响是对细胞环境的响应。这些比较的遗传结果支持细胞-基因-环境相互作用的概念。