University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD.
University of Maryland, School of Medicine, Department of Radiation Oncology, Baltimore, MD.
Health Phys. 2020 Nov;119(5):621-632. doi: 10.1097/HP.0000000000001350.
High-dose radiation exposure results in organ-specific sequelae that occurs in a time- and dose-dependent manner. The partial body irradiation with minimal bone marrow sparing model was developed to mimic intentional or accidental radiation exposures in humans where bone marrow sparing is likely and permits the concurrent analysis of coincident short- and long-term damage to organ systems. To help inform on the natural history of the radiation-induced injury of the partial body irradiation model, we quantitatively profiled the plasma proteome of non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing with 6 MV LINAC-derived photons at 0.80 Gy min over a time period of 3 wk. The plasma proteome was analyzed by liquid chromatography-tandem mass spectrometry. A number of trends were identified in the proteomic data including pronounced protein changes as well as protein changes that were consistently upregulated or downregulated at all time points and dose levels interrogated. Pathway and gene ontology analysis were performed; bioinformatic analysis revealed significant pathway and biological process perturbations post high-dose irradiation and shed light on underlying mechanisms of radiation damage. Additionally, proteins were identified that had the greatest potential to serve as biomarkers for radiation exposure.
高剂量辐射暴露会导致特定器官的后遗症，其发生方式具有时间和剂量依赖性。最小骨髓保留的全身部分照射模型的开发是为了模拟人类中可能发生的故意或意外辐射暴露，并允许同时分析器官系统的短期和长期并发损伤。为了帮助了解全身部分照射模型的辐射损伤的自然史，我们对接受 12Gy 全身部分照射的非人类灵长类动物的血浆蛋白质组进行了定量分析，该模型采用 6MV LINAC 衍生的光子进行照射，骨髓保留率为 2.5%，剂量率为 0.80Gy/min，时间跨度为 3 周。通过液相色谱-串联质谱法分析血浆蛋白质组。在蛋白质组数据中发现了一些趋势，包括明显的蛋白质变化，以及在所有时间点和剂量水平检测到的一致上调或下调的蛋白质变化。进行了途径和基因本体分析；生物信息学分析显示，高剂量照射后显著改变了途径和生物学过程，并揭示了辐射损伤的潜在机制。此外，还鉴定出了一些具有最大潜力作为辐射暴露生物标志物的蛋白质。
