Global gene expression and Ingenuity biological functions analysis on PCBs 153 and 138 induced human PBMC in vitro reveals differential mode(s) of action in developing toxicities.
Global gene expression and Ingenuity biological functions analysis on PCBs 153 and 138 induced human PBMC in vitro reveals differential mode(s) of action in developing toxicities.
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DOI：
10.1016/j.envint.2011.02.010
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发表时间：
2011-07
影响因子：
11.8
通讯作者：
Dutta, Sisir K.
中科院分区：
文献类型：
--
作者：
Ghosh, Somiranjan;Zang, Shizhu;Mitra, Partha S.;Ghimbovschi, Svetlana;Hoffman, Eric P.;Dutta, Sisir K.
一些报告表明，低水平的多氯联苯（PCB）接触可以在体外、体内以及流行病学研究中报告的多种生理紊乱和疾病产生不利影响。这项调查的重点是可能的贡献，两个最普遍的多氯联苯同系物在体外发展毒性。我们使用人体等效水平的PCB 138和153作为模型药物来测试其特异性。我们选择了一个全球性的方法，使用寡核苷酸微阵列技术来调查调制基因表达的生物学效应，暴露后的多氯联苯，随后的免疫途径分析（IPA），了解潜在的后果，在发展中的疾病和障碍。我们用人外周血单核细胞（PBMC）进行了体外研究，其中PBMC细胞暴露于相应的PCB 48小时。总的来说，我们对基因表达的观察表明，PCB产生一个独特的签名，影响不同的途径，具体为每一个同源物。在通过IPA分析这些数据时，突出和有趣的疾病和障碍是神经系统疾病、癌症、心血管疾病、呼吸系统疾病以及内分泌系统疾病、遗传疾病和生殖系统疾病。它们在体外、体内和流行病学研究中表现出很强的相似性。在肾脏和泌尿系统疾病、器官损伤和异常、牙科疾病、眼科疾病和心理障碍方面观察到明显的差异，这些疾病仅通过接触PCB 138而不是PCB 153来揭示。本研究强调了体外整体基因表达的挑战，并与暴露人群的结果相关。微阵列结果给出了PCB暴露后的分子机制和功能效应。与几种可能的作用模式相关的基因变化程度突出了细胞功能和发挥主要作用的信号通路的变化。除了了解与化学品的作用方式有关的途径外，这些数据还可导致确定基因组特征，可用于筛选化学品是否有可能导致疾病和发育障碍。
Several reports have indicated that low level of polychlorinated biphenyl (PCB) exposure can adversely affect a multitude of physiological disorders and diseases in in vitro, in vivo, and as reported in epidemiological studies. This investigation is focused on the possible contribution of two most prevalent PCB congeners in vitro in developing toxicities. We used PCB 138 and 153 at the human equivalence level as model agents to test their specificity. We chose a global approach using oligonucleotide microarray technology to investigate modulated gene expression for biological effects, upon exposure of PCBs, followed by Ingenuity Pathway Analysis (IPA), to understand the underlying consequence in developing disease and disorders. We performed in vitro studies with human peripheral blood mononuclear cells (PBMC), where PBMC cells were exposed to respective PCBs for 48 hrs. Overall, our observation on gene expression indicated that PCB produces a unique signature affecting different pathways, specific for each congener. While analyzing these data through IPA, the prominent and interesting disease and disorders were Neurological disease, Cancer, Cardiovascular disease, respiratory disease, as well as endocrine system disorders Genetic disorders, and reproductive system disease. They showed strong resemblances with in vitro, in vivo, and in the epidemiological studies. A distinct difference was observed in renal and urological diseases, organisimal injury and abnormalities, dental disease, ophthalmic disease, and psychological disorders, which are only revealed by PCB 138 exposure, but not in PCB 153. The present study emphasizes the challenges of global gene expression in vitro and was correlated with the results of exposed human population. The microarray results give a molecular mechanistic insight and functional effects, following PCB exposure. The extent of changes in genes related to several possible mode(s) of action highlights the changes in cellular functions and signaling pathways that play major roles. In addition to understanding the pathways related to mode of action for chemicals, these data could lead to the identification of genomic signatures that could be used for screening of chemicals for their potential to cause disease and developmental disorders.
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影响因子：
10.4
作者：
Fitzgerald EF;Hwang SA;Lambert G;Gomez M;Tarbell A
通讯作者：
Tarbell A
影响因子：
3
作者：
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通讯作者：
Trnovec, T.
DOI：
10.1080/10253890701314863
发表时间：
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影响因子：
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作者：
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作者：
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作者：
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