Associations of Benzo(ghi)perylene and Heptachlorodibenzo-p-dioxin in Serum of Service Personnel Deployed to Balad, Iraq, and Bagram, Afghanistan Correlates With Perturbed Amino Acid Metabolism in Human Lung Fibroblasts

• Type of Material: Article
• Authors: Matthew Smith, Emory University; Collynn F. Woeller, University of Rochester; Karan Uppal, Emory University; Thomas H. Thatcher, University of Rochester; Douglas Walker, Emory University; Philip K. Hopke, University of Rochester; Patricia Rohrbeck, Armed Forces Health Surveillance Center; Timothy M. Mallon, Uniformed Services University of the Health Sciences; Pamela L. Krahl, Uniformed Services University of the Health Sciences; Mark J. Utell, University of Rochester; Young-Mi Go, Emory University; Dean Jones, Emory University
• Language: English
• Date: 2019-12-01
• Publisher: Lippincott Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 by the American College of Occupational and Environmental Medicine
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/JOM.0000000000001669
• Title of Journal or Parent Work: Journal of Occupational and Environmental Medicine
• Volume: 61
• Issue: 12
• Start Page: S35
• End Page: S44
• Grant/Funding Information: This public health surveillance project was supported by funding from the Department of Defense award (306889-1.00-64239), and National Institute of Health (award R01 ES023485, P30 ES019776 and S10 OD 018006).
• Keywords: Receptors; Life Sciences & Biomedicine; Science & Technology; Metabolomics; Polycyclic aromatic hydrocarbons; Health; Public, Environmental & Occupational Health; Cells; high-resolution metabolomics; environmental toxicology; Expression; exposome; Micronas; exposure bio-monitoring; Exposure
• Research Categories: Environmental Sciences; Health Sciences, Occupational Health and Safety; Health Sciences, Medicine and Surgery; Health Sciences, Public Health

Abstract

Objective: A study was conducted to identify metabolic-related effects of benzo(ghi)perylene (BghiP) and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD), on primary human fibroblasts to verify biological associations previously found in occupational health research. Methods: Human lung fibroblasts were exposed to BghiP or HpCDD and extracts were analyzed with a metabolome-wide association study to test for pathways and metabolites altered relative to controls. Gene expression was measured by quantitative-real time polymerase chain reaction. Results: Metabolic perturbations in amino-acid, oxidative stress, and fatty-acid pathways were observed for BghiP and HpCDD. HpCDD but not BghiP exposure increased gene expression of the amino acid transporters SLC7A5 and SLC7A11. Conclusions: Exposure to polycyclic aromatic hydrocarbons (PAH) or dioxins perturbs amino acid pathways at physiologically relevant concentrations with different mechanisms. These findings imply an effect on central homeostatic systems by environmental exposures which could have implications on disease susceptibility.