title: Gas Chromatography/Mass Spectrometry Metabolomics of Urine and Serum from Nonhuman Primates Exposed to Ionizing Radiation: Impacts on the Tricarboxylic Acid Cycle and Protein Metabolism.
abstract: Ionizing radiation (IR) directly damages cells and tissues or indirectly damages them through reactive free radicals that may lead to longer term adverse sequelae such as cancers, persistent inflammation, or possible death. Potential exposures include nuclear reactor accidents, improper disposal of equipment containing radioactive materials or medical errors, and terrorist attacks. Metabolomics (comprehensive analysis of compounds <1 kDa) by mass spectrometry (MS) has been proposed as a tool for high-throughput biodosimetry and rapid assessment of exposed dose and triage needed. While multiple studies have been dedicated to radiation biomarker discovery, many have utilized liquid chromatography (LC) MS platforms that may not detect particular compounds (e.g., small carboxylic acids or isomers) that complementary analytical tools, such as gas chromatography (GC) time-of-flight (TOF) MS, are ideal for. The current study uses global GC-TOF-MS metabolomics to complement previous LC-MS analyses on nonhuman primate biofluids (urine and serum) 7 days after exposure to 2, 4, 6, 7, and 10 Gy IR. Multivariate data analysis was used to visualize differences between control and IR exposed groups. Univariate analysis was used to determine a combined 26 biomarkers in urine and serum that significantly changed after exposure to IR. We found several metabolites involved in tricarboxylic acid cycle function, amino acid metabolism, and host microbiota that were not previously detected by global and targeted LC-MS studies.
authors.affiliation: Tumor Biology Program, Lombardi Comprehensive Cancer Center, Georgetown University , Washington, D.C. 20057, United States.
authors.forename: Evan L
authors.identifier: 0000-0002-4953-9715
authors.initials: EL
authors.lastname: Pannkuk
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center , Washington, D.C. 20057, United States.
authors.forename: Evagelia C
authors.initials: EC
authors.lastname: Laiakis
authors.affiliation: CiToxLAB North America , Laval, Quebec H7V 4B3, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Authier
authors.affiliation: CiToxLAB North America , Laval, Quebec H7V 4B3, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Wong
authors.affiliation: Tumor Biology Program, Lombardi Comprehensive Cancer Center, Georgetown University , Washington, D.C. 20057, United States.|Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center , Washington, D.C. 20057, United States.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Fornace
mesh_terms: D000596:Amino Acids / Q000378:metabolism / Q000528:radiation effects; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002952:Citric Acid Cycle / Q000528:radiation effects; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D055432:Metabolomics / Q000379:methods*; D064307:Microbiota / Q000528:radiation effects; D011323:Primates; D011506:Proteins / Q000378:metabolism / Q000528:radiation effects; D011839:Radiation, Ionizing; D044967:Serum / Q000737:chemistry*; D014556:Urine / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D011506:Proteins
keywords: gas chromatography; ionizing radiation; mass spectrometry; metabolomics; nonhuman primate