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

E. Drizik; S. Corbett; Y. Zheng; R. Vermeulen; Y. Dai; W. Hu; D. Ren; H. Duan; Y. Niu; J. Xu; W. Fu; K. Meliefste; B. Zhou; Xiaohui Zhang; J. Yang; Bryan Bassig; Hanqiao Liu; M. Ye; Gang Liu; X. Jia; T. Meng; P. Bin; J. Zhang; D. Silverman; A. Spira; N. Rothman; M.E. Lenburg; Q. Lan

Environment International (Apr 2020)

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

E. Drizik,
S. Corbett,
Y. Zheng,
R. Vermeulen,
Y. Dai,
W. Hu,
D. Ren,
H. Duan,
Y. Niu,
J. Xu,
W. Fu,
K. Meliefste,
B. Zhou,
Xiaohui Zhang,
J. Yang,
Bryan Bassig,
Hanqiao Liu,
M. Ye,
Gang Liu,
X. Jia,
T. Meng,
P. Bin,
J. Zhang,
D. Silverman,
A. Spira,
N. Rothman,
M.E. Lenburg,
Q. Lan

Affiliations

E. Drizik: Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
S. Corbett: Bioinformatics Program, Boston University, Boston, MA, USA
Y. Zheng: Key Laboratory of Chemical Safety and Health, National Institute of Occupational, Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China; Corresponding authors at: Key Laboratory of Chemical Safety and Health, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China (Y. Zheng). Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA (M.E. Lenburg).
R. Vermeulen: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
Y. Dai: Key Laboratory of Chemical Safety and Health, National Institute of Occupational, Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China
W. Hu: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
D. Ren: Chaoyang Center for Disease Control and Prevention, Chaoyang, China
H. Duan: Key Laboratory of Chemical Safety and Health, National Institute of Occupational, Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China
Y. Niu: Key Laboratory of Chemical Safety and Health, National Institute of Occupational, Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China
J. Xu: Hong Kong University, Hong Kong, China
W. Fu: Chaoyang Center for Disease Control and Prevention, Chaoyang, China
K. Meliefste: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
B. Zhou: Key Laboratory of Chemical Safety and Health, National Institute of Occupational, Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China
Xiaohui Zhang: Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
J. Yang: Chaoyang Center for Disease Control and Prevention, Chaoyang, China
Bryan Bassig: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
Hanqiao Liu: Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
M. Ye: Key Laboratory of Chemical Safety and Health, National Institute of Occupational, Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China
Gang Liu: Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
X. Jia: Key Laboratory of Chemical Safety and Health, National Institute of Occupational, Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China
T. Meng: Key Laboratory of Chemical Safety and Health, National Institute of Occupational, Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China
P. Bin: Key Laboratory of Chemical Safety and Health, National Institute of Occupational, Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China
J. Zhang: Nicholas School of the Environment and Duke Global Health Institute, Duke University, Durham, NC, USA; Global Health Research Center, Duke Kunshan University, Kunshan City, Jiangsu Province, China
D. Silverman: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
A. Spira: Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA; Bioinformatics Program, Boston University, Boston, MA, USA; The Lung Cancer Initiative at Johnson & Johnson, Cambridge, MA, USA
N. Rothman: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
M.E. Lenburg: Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA; Bioinformatics Program, Boston University, Boston, MA, USA; Corresponding authors at: Key Laboratory of Chemical Safety and Health, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China (Y. Zheng). Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA (M.E. Lenburg).
Q. Lan: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA

Journal volume & issue: Vol. 137

Abstract

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Background: Diesel engine exhaust (DEE) exposure causes lung cancer, but the molecular mechanisms by which this occurs are not well understood. Objectives: 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 exposed to relatively high levels of DEE (17.2–105.4 μg/m3), and 38 unexposed workers from factories without DEE exposure. mRNA was profiled for gene expression using Affymetrix microarrays. Linear modeling was used to identify differentially expressed genes associated with DEE exposure and interaction effects with current smoking status. Pathway enrichment among differentially expressed genes was assessed using EnrichR. Gene Set Enrichment Analysis (GSEA) was used to compare gene expression patterns between datasets. Results: 225 genes had expression associated with DEE exposure after adjusting for smoking status (FDR q < 0.25) and were enriched for genes in pathways related to oxidative stress response, cell cycle pathways such as MAPK/ERK, protein modification, and transmembrane transport. Genes up-regulated in DEE-exposed individuals were enriched among the genes most up-regulated by cigarette smoking in a previously reported bronchial airway smoking dataset. We also found that the DEE signature was enriched among the genes most altered in two previous studies of the effects of acute DEE on PBMC gene expression. An exposure-response relationship was demonstrated between air levels of elemental carbon and the first principal component of the DEE signature. Conclusions: A gene expression signature was identified for workers occupationally exposed to DEE that was altered in an exposure-dependent manner and had some overlap with the effects of smoking and the effects of acute DEE exposure. This is the first study of gene expression in nasal epithelial cells of workers heavily exposed to DEE and provides new insights into the molecular alterations that occur with DEE exposure. Keywords: Diesel engine exhaust, Microarray, Lung cancer, Occupational exposure

Published in Environment International

ISSN: 0160-4120 (Print)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/environment-international

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