Title: 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.
Authors: Smith, Matthew Ryan; Woeller, Collynn F; Uppal, Karan; Thatcher, Thomas H; Walker, Douglas I; Hopke, Philip K; Rohrbeck, Patricia; Mallon, Timothy M; Krahl, Pamela L; Utell, Mark J; Go, Young-Mi; Jones, Dean P
Published In J Occup Environ Med, (2019 12)
Abstract: 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.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.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.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.
PubMed ID: 31800449
MeSH Terms: Afghan Campaign 2001-*; Amino Acids/metabolism*; Cells, Cultured; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Environmental Exposure/adverse effects; Environmental Exposure/statistics & numerical data; Fibroblasts/drug effects*; Fibroblasts/metabolism; Humans; Iraq War, 2003-2011*; Lung/drug effects*; Lung/metabolism; Mass Spectrometry; Metabolomics; Military Personnel/statistics & numerical data*; Perylene/adverse effects; Perylene/analogs & derivatives*; Perylene/blood; Polychlorinated Dibenzodioxins/adverse effects; Polychlorinated Dibenzodioxins/blood*; Real-Time Polymerase Chain Reaction; United States