Pannkuk Evan L, Laiakis Evagelia C, Mak Tytus D, Astarita Giuseppe, Authier Simon, Wong Karen, Fornace Albert J
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC.
Mass Spectrometry Data Center, National Institute of Standards and Technology, Gaithersburg, MD.
Metabolomics. 2016 May;12(5). doi: 10.1007/s11306-016-1010-0. Epub 2016 Mar 15.
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.
The current study assesses changes in the nonhuman primate (NHP) serum lipidome and metabolome 7 days following exposure to ionizing radiation (IR).
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.
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.
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.
由于核能潜在事故和恐怖主义威胁带来的危险，需要高通量生物剂量测定法来快速评估个体辐射暴露剂量。脂质组学和代谢组学正成为确定疾病或其他身体损伤后整体特征的常用工具，并提供潜在细胞损伤的“快照”。
本研究评估了非人灵长类动物（NHP）暴露于电离辐射（IR）7天后血清脂质组和代谢组的变化。
采用双相液液萃取法提取血清样本中的脂质和代谢物，并通过超高效液相色谱四极杆飞行时间质谱进行分析。以数据独立模式获取整体辐射特征。
辐射暴露导致脂质代谢发生显著扰动，影响所有主要脂质种类，包括游离脂肪酸、甘油脂、甘油磷脂和酯化固醇。特别是，我们观察到暴露于10 Gy辐射的NHP血清中含多不饱和脂肪酸（PUFA）的脂质水平显著升高，表明PUFA在对IR的生理反应中起主要作用。代谢组学分析表明，暴露于10 Gy辐射的NHP血清中氨基酸、肉碱和嘌呤代谢物水平升高，表明蛋白质消化/吸收、生物氧化和脂肪酸β氧化受到扰动。
这是第一份确定辐射暴露后NHP血清整体脂质组和代谢组变化的报告，并为基于人类的生物剂量测定中开发代谢组学生物标志物面板提供了信息。
