Abstract 4256: Impact of diesel engine exhaust exposure on the airway transcriptome

Abstract

Abstract Rationale: Recent epidemiological studies show that Diesel Engine Exhaust (DEE) exposure is associated with lung cancer, however the mechanism by which this occurs is not well understood. The goal of this study was to assess the transcriptomic alterations in the nasal epithelium of DEE exposed workers from factories where diesel engines are utilized. Methods: Nasal epithelium brushings were obtained from 41 subjects who work in a factory with DEE exposure, and 38 comparable control subjects who work in factories without any DEE exposure. The median Elemental Carbon (EC) levels of exposed individuals was 60.7μg/m3, with a range of 17.2-105.4 μg/m3, respectively. RNA was isolated from nasal epithelial cells, and profiled for gene expression using Affymetrix microarrays. Linear modeling was used to detect differential expression between DEE exposure and controls. Pathway enrichment in differentially expressed genes was assessed using GO Biological Process and KEGG terms via EnrichR. Results: We found 234 genes that were differentially expressed between samples derived from DEE exposed participants versus controls at FDR q < 0.25. Within this set of genes, we observed a higher expression of genes involved in oxidative stress response, as well as cell proliferation, cellular transcription, and regulation of apoptosis. In addition, we found that genes involved in ion transport, such as CFTR, were expressed at lower levels in DEE exposed samples. Conclusions: Chronic DEE exposure associates with changes in the airway transcriptome, with increased stress response as a major effect of DEE exposure. The transcriptomic alterations we identified may help provide insight into the underlying mechanisms of DEE carcinogenicity. Citation Format: Eduard I. Drizik, Sean Corbett, Roel Vermeulen, Yufei Dai, Wei Hu, Marc Lenburg, Dianzhi Ren, Huawei Duan, Yong Niu, Jun Xu, Wei Fu, Kees Meliefste, Baosen Zhou, JuFang Yang, Meng Ye, Xiaowei Jia, Tao Meng, Ping Bin, Yuxin Zheng, Debra Silverman, Nathaniel Rothman, Avrum Spira, Qing Lan. Impact of diesel engine exhaust exposure on the airway transcriptome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4256. doi:10.1158/1538-7445.AM2017-4256