title: A Lipidomic and Metabolomic Serum Signature from Nonhuman Primates Exposed to Ionizing Radiation.
abstract: BACKGROUND
  Due to dangers associated with potential accidents from nuclear energy and terrorist threats, there is a need for high-throughput biodosimetry to rapidly assess individual doses of radiation exposure. Lipidomics and metabolomics are becoming common tools for determining global signatures after disease or other physical insult and provide a "snapshot" of potential cellular damage.
  
  
  OBJECTIVE
  The current study assesses changes in the nonhuman primate (NHP) serum lipidome and metabolome 7 days following exposure to ionizing radiation (IR).
  
  
  METHODS
  Serum sample lipids and metabolites were extracted using a biphasic liquid-liquid extraction and analyzed by ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry. Global radiation signatures were acquired in data-independent mode.
  
  
  RESULTS
  Radiation exposure caused significant perturbations in lipid metabolism, affecting all major lipid species, including free fatty acids, glycerolipids, glycerophospholipids and esterified sterols. In particular, we observed a significant increase in the levels of polyunsaturated fatty acids (PUFA)-containing lipids in the serum of NHPs exposed to 10 Gy radiation, suggesting a primary role played by PUFAs in the physiological response to IR. Metabolomics profiling indicated an increase in the levels of amino acids, carnitine, and purine metabolites in the serum of NHPs exposed to 10 Gy radiation, suggesting perturbations to protein digestion/absorption, biological oxidations, and fatty acid β-oxidation.
  
  
  CONCLUSIONS
  This is the first report to determine changes in the global NHP serum lipidome and metabolome following radiation exposure and provides information for developing metabolomic biomarker panels in human-based biodosimetry.
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC.
authors.forename: Evan L
authors.initials: EL
authors.lastname: Pannkuk
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC.
authors.forename: Evagelia C
authors.initials: EC
authors.lastname: Laiakis
authors.affiliation: Mass Spectrometry Data Center, National Institute of Standards and Technology, Gaithersburg, MD.
authors.forename: Tytus D
authors.initials: TD
authors.lastname: Mak
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC; Health Sciences, Waters Corporation, Milford, MA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Astarita
authors.affiliation: CiToxLAB North America, Laval, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Authier
authors.affiliation: CiToxLAB North America, Laval, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Wong
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC; Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC; Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Fornace
keywords: Ionizing Radiation; Lipidomics; Metabolomics; Nonhuman Primate