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Proteomic, Metabolomic, and Lipidomic Analyses of Lung Tissue Exposed to Mustard Gas

Elizabeth Dhummakupt, Conor Jenkins, Gabrielle Rizzo, Allison Melka, Daniel Carmany, Amber Prugh, Jennifer Horsmon, Julie Renner and Daniel Angelini
Abstract

Sulfur mustard (HD) poses a serious threat due to its relatively simple production process. Exposure to HD in the short-term causes an inflammatory response, while long-term exposure results in DNA and RNA damage. Respiratory tract tissue models were exposed to relatively low concentrations of HD and collected at 3 and 24 h post exposure. Histology, cytokine ELISAs, and mass spectrometric-based analyses were performed. Histology and ELISA data confirmed previously seen lung damage and inflammatory markers from HD exposure. The multi-omic mass spectrometry data showed variation in proteins and metabolites associated with increased inflammation, as well as DNA and RNA damage. HD exposure causes DNA and RNA damage that results in variation of proteins and metabolites that are associated with transcription, translation and cellular energy.

Keywords

EpiAirway (AIR-100-HCF), DNA damage, RNA damage, histology, MTT, inflammation, lipids, sulfur mustard, mustard gas, HD, proteomic analysis, metabolomic analysis, lipidomic analysis, IL-1a, IL-1b, IL-6, TNF-a, corn oil, chromosomal mapping, plasminogen activator inhibitor 2 (PAI2), urokinase-type plasminogen activator receptor (uPAR), Urokinase plasminogen activator surface receptor, tissue factor pathway inhibitor (TFPI), pathway network mapping, base excision repair, DNA repair (POLB, POLL), DNA synthesis (POLE), poly(ADP-ribose)polymerase (PARP), proliferating cell nuclear antigen (PCNA), DNA-apurinc or apyrimidinic site endonuclease 2 (APEX2), high mobility group protein B1 (HMGB1), TIMP1, MMP9, TDP-43 protein, nucleotide metabolism, adenine, adenosine, AMP, ADP, IMP, Inosine, hypoxanthine, sphingomyelin, ceramide, pyknotic nuclei, karyorrhexes nuclei, apoptotic cells, TNFAIP3, TNFSF9, TNFRSF10A, TNFRSF10B, phosphocholine, phosphatidylcholine, acetylcholine, acetylcarnitine, ribonucleotide, ribose phosphate, ribonucleotide biosynthetic and metabolic pathways, Dom34, PABP1, MSL1, nicotinamide

Materials Tested

sulfur mustard, mustard gas

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