Benzo[a]pyrene Perturbs Mitochondrial and Amino Acid Metabolism in Lung Epithelial Cells and Has Similar Correlations With Metabolic Changes in Human Serum.

Abstract

OBJECTIVE A study was conducted to identifymetabolic-related effects of benzo[a]pyrene (BaP) on human lung epithelial cells and validate these findings using human sera. METHODS Human lung epithelial cells were treated with BaP, and extracts were analyzed with a global metabolome-wide association study (MWAS) to test for pathways and metabolites altered relative to vehicle controls. RESULTS MWAS results showed that BaP metabolites were among the top metabolites differing between BaP-treated cells and controls. Pathway enrichment analysis further confirmed that fatty acid, lipid, and mitochondrial pathways were altered by BaP. Human sera analysis showed that lipids varied with BaP concentration. BaP associations with amino acid metabolism were found in both models. CONCLUSIONS These findings show that BaP has broad metabolic effects, and suggest that air pollution exacerbates disease processes by altered mitochondrial and amino acid metabolism.