Transcriptomic changes in the nasal epithelium associated with diesel engine exhaust exposure

Abstract

RATIONALE: Epidemiological studies,show that chronic diesel engine exhaust (DEE) exposure in oocupational settings is associated with lung cancer and other airway diseases. However, the molecular mechanisms by whiich this occurs is not well understood. The goal of this study was to assess transcriptomic alterations in nasal epithelium of DEE exposed factory workers to better understand the cellular and molecular effects of DEE. METHODS: Nasal epithelial brushings were obtained from 41 diesel engine factory workers with known DEE exposure, as well as 38 control subjects who work in factories without DEE exposure. Total RNA was isolated from these samples, and profiled for gene expression using Affymetrix microarrays. Linear modeling was used to identify genes differentially expressed between DEE exposed and control subjects, as well as identifying interaction effects between DEE and active smoking status. Pathway enrichment in differentially expressed genes was assessed using EnrichR. Gene Set Enrichment Analysis (GSEA) was used to compare gene expression patterns across datasets. RESULTS: We found 225 genes whose expression is associated with DEE exposure at FDR q < 0.25, after adjusting for smoking status. These genes were enriched in pathways related to oxidative stress response, cell cycle, and protein modification, as well as transmembrane transport genes, such as CFTR. We further demonstrated that genes up-regulated in the DEE signature are enriched amongst the genes most upregulated by smoking in a previously published dataset. CONCLUSIONS: We characterized the gene expression alterations, resulting from occupational diesel engine exhaust exposure, in the nasal epithelium, including identifying the altered expression of genes involved in xenobiotic metabolism and oxidative stress response. The transcriptomic alterations we identified in the nasal airway may provide insight into airwaydisease pathogenesis and determine differences as well as commonalities in the response of airway epithelium to different inhaled toxins. This abstract is funded by: National Cancer Institute