Tumor Biology Program, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C., 20057, USA.
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, D.C., 20057, USA.
Sci Rep. 2017 Aug 29;7(1):9777. doi: 10.1038/s41598-017-10299-w.
Concern over potential exposures of ionizing radiation (IR) to large populations has emphasized the need for rapid and reliable methods of biodosimetry to determine absorbed dose and required triage. Lipidomics has emerged as a powerful technique for large-scale lipid identification and quantification. Indirect effects from IR exposure generate reactive oxygen species (ROS) through water hydrolysis and may subsequently damage cellular lipids. Thus, rapid identification of specific affected lipid molecules represents possible targets for biodosimetry. The current study addresses temporal changes in the serum lipidome from 4 h to 28 d in nonhuman primates (NHPs) with radiation-induced hematopoietic syndrome (6.5 Gy exposure, LD). Statistical analyses revealed a highly dynamic temporal response in the serum lipidome after IR exposure. Marked lipidomic perturbations occurred within 24 h post-irradiation along with increases in cytokine levels and C-reactive protein. Decreases were observed in di- and triacylglycerides, sphingomyelins (SMs), lysophosphatidylcholines (LysoPCs), and esterified sterols. Conversely, free fatty acids and monoacylglycerides significantly increased. Decreased levels of SMs and increased levels of LysoPCs may be important markers for biodosimetry ~2 d-3 d post-irradiation. The biphasic and dynamic response to the serum lipidome post-irradiation emphasize the importance of determining the temporal long-term response of possible radiation markers.
人们对大群体可能接触电离辐射 (IR) 的担忧强调了需要快速可靠的生物剂量测定方法来确定吸收剂量和所需的分类。脂质组学已成为大规模脂质鉴定和定量的有力技术。IR 暴露的间接影响通过水水解产生活性氧 (ROS)，并可能随后破坏细胞脂质。因此，快速鉴定特定受影响的脂质分子代表了生物剂量测定的可能靶标。本研究在具有辐射诱导造血综合征 (6.5Gy 暴露，LD) 的非人类灵长类动物 (NHPs) 中，从 4 小时到 28 天，研究了血清脂质组的时间变化。统计分析显示，IR 暴露后血清脂质组呈现出高度动态的时间响应。在辐照后 24 小时内观察到明显的脂质组学扰动，同时细胞因子水平和 C 反应蛋白增加。二酰基甘油、鞘磷脂 (SM)、溶血磷脂酰胆碱 (LysoPC) 和酯化甾醇减少。相反，游离脂肪酸和单酰基甘油显著增加。SM 水平降低和 LysoPC 水平升高可能是辐照后 2-3 天生物剂量测定的重要标志物。辐照后血清脂质组的双相和动态反应强调了确定可能的辐射标志物的时间长期反应的重要性。
