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Carcinogenic Effects of Oil Dispersants: a KEGG Pathway-based RNA-seq Study of Human Airway Epithelial Cells

机译:油分散剂的致癌作用:基于KEGG通路的人气道上皮细胞的RNA-seq研究

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摘要

The health impacts of the BP oil spill are yet to be further revealed as the toxicological effects of oil products and dispersants on human respiratory system may be latent and complex, and hence difficult to study and follow up. Here we performed RNA-seq analyses of a system of human airway epithelial cells treated with the BP crude oil and/or dispersants Corexit 9500 and Corexit 9527 that were used to help break up the oil spill. Based on the RNA-seq data, we then systemically analyzed the transcriptomic perturbations of the cells at the KEGG pathway level using two pathway-based analysis tools, GAGE (generally applicable gene set enrichment) and GSNCA (Gene Sets Net Correlations Analysis). Our results suggested a pattern of change towards carcinogenesis for the treated cells marked by upregulation of ribosomal biosynthesis (hsa03008) (p = 1.97e-13), protein processing (hsa04141) (p = 4.09e-7), Wnt signaling (hsa04310) (p = 6.76e-3), neurotrophin signaling (hsa04722) (p = 7.73e-3) and insulin signaling (hsa04910) (p = 1.16e-2) pathways under the dispersant Corexit 9527 treatment, as identified by GAGE analysis. Furthermore, through GSNCA analysis, we identified gene co-expression changes for several KEGG cancer pathways, including small cell lung cancer pathway (hsa05222, p = 9.99e-5), under various treatments of oil/dispersant, especially the mixture of oil and Corexit 9527. Overall, our results suggested carcinogenic effects of dispersants (in particular Corexit 9527) and their mixtures with the BP crude oil, and provided further support for more stringent safety precautions and regulations for operations involving long-term respiratory exposure to oil and dispersants.
机译:由于石油产品和分散剂对人体呼吸系统的毒理作用可能是潜在的和复杂的,因此难以研究和跟进,因此BP石油泄漏对健康的影响有待进一步揭示。在这里,我们对使用BP原油和/或分散剂Corexit 9500和Corexit 9527处理过的人类气道上皮细胞系统进行了RNA-seq分析,这些系统用于帮助打破溢油。基于RNA-seq数据,我们然后使用两种基于途径的分析工具GAGE(通常适用的基因集富集)和GSNCA(基因集净相关分析)在KEGG途径水平上系统分析了细胞的转录组扰动。我们的结果表明,以核糖体生物合成(hsa03008)(p = 1.97e-13),蛋白质加工(hsa04141)(p = 4.09e-7),Wnt信号传导(hsa04310)上调为特征的处理细胞向致癌性的变化模式(p = 6.76e-3),神经营养蛋白信号转导(hsa04722)(p = 7.73e-3)和胰岛素信号转导(hsa04910)(p = 1.16e-2)途径在Corexit 9527分散剂处理下进行,通过GAGE分析确定。此外,通过GSNCA分析,我们确定了在多种油/分散剂处理下,特别是油和油的混合物,几种KEGG癌症途径(包括小细胞肺癌途径(hsa05222,p = 9.99e-5))的基因共表达变化。 Corexit9527。总体而言,我们的结果表明分散剂(特别是Corexit 9527)及其与BP原油的混合物的致癌作用,并为涉及长期呼吸暴露于油和分散剂的操作提供了更严格的安全预防措施和法规提供了进一步的支持。

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