Abstract
Introduction
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.
Objectives
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.
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Acknowledgments
The authors acknowledge Lombardi Comprehensive Cancer Proteomics and Metabolomics Shared Resource (PMSR) for data acquisition. Content is the responsibility of authors and does not necessarily represent official views of NCI/NIH.
Funding
National Institutes of Health (National Institute of Allergy and Infectious Diseases) grant 1R01AI101798 (P.I. Albert J. Fornace, Jr.) and Lombardi Comprehensive Cancer Proteomics and Metabolomics Shared Resource (PMSR); partial support National Cancer Institute grant P30CA051008 (P.I. Louis Weiner).
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Evan L. Pannkuk, Evagelia C. Laiakis, Tytus D. Mak, Giuseppe Astarita, Simon Authier, Karen Wong, and Albert J. Fornace Jr. declare that they have no conflict of interest.
Ethics Approval
NHP studies were conducted by CiToxLAB: North America Safety and Health Research Laboratories (Laval, Québec, Canada; study # 5013-0193) and was approved by the Institutional Animal Care and Use Committee.
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Pannkuk, E.L., Laiakis, E.C., Mak, T.D. et al. A lipidomic and metabolomic serum signature from nonhuman primates exposed to ionizing radiation. Metabolomics 12, 80 (2016). https://doi.org/10.1007/s11306-016-1010-0
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DOI: https://doi.org/10.1007/s11306-016-1010-0