title: Carcinogenic effects of oil dispersants: A KEGG pathway-based RNA-seq study of human airway epithelial cells.
abstract: 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.
authors.affiliation: Dept. of Global Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA. Electronic address: yliu8@tulane.edu.
authors.forename: Yao-Zhong
authors.initials: YZ
authors.lastname: Liu
authors.affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College, Soochow University, Su Zhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Dept. of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Roy-Engel
authors.affiliation: Dept. of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Saito
authors.affiliation: Dept. of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Lasky
authors.affiliation: Dept. of Chemistry, RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA, USA.
authors.forename: Guangdi
authors.initials: G
authors.lastname: Wang
authors.affiliation: Dept. of Chronic Respiratory Diseases, School of Health Sciences, University of Newcastle, Callaghan, Australia.
authors.forename: He
authors.initials: H
authors.lastname: Wang
mesh_terms: D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000633:toxicity*; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D010578:Petroleum / Q000633:toxicity*; D059392:Petroleum Pollution / Q000009:adverse effects*; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000187:drug effects; D013501:Surface-Active Agents / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D002273:Carcinogens; D008055:Lipids; D010578:Petroleum; D013501:Surface-Active Agents; D014874:Water Pollutants, Chemical; C470995:corexit 9500; C021984:corexit 9527
keywords: Airway epithelial cells; BP oil spill; Carcinogenesis; Dispersants; GAGE; GSNCA; KEGG; Oil; RNA-seq