Time- and radiation-dose dependent changes in the plasma proteome after total body irradiation of non-human primates: Implications for biomarker selection

Acute radiation syndrome (ARS) is a complex multi-organ disease resulting from total body exposure to high doses of radiation. Individuals can be exposed to total body irradiation (TBI) in a number of ways, including terrorist radiological weapons or nuclear accidents. In order to determine whether an individual has been exposed to high doses of radiation and needs countermeasure treatment, robust biomarkers are needed to estimate radiation exposure from biospecimens such as blood or urine. In order to identity such candidate biomarkers of radiation exposure, high-resolution proteomics was used to analyze plasma from non-human primates following whole body irradiation (Co-60 at 6.7 Gy and 7.4 Gy) with a twelve day observation period. A total of 663 proteins were evaluated from the plasma proteome analysis. A panel of plasma proteins with characteristic time- and dose-dependent changes was identified. In addition to the plasma proteomics study reported here, we recently identified candidate biomarkers using urine from these same non-human primates. From the proteomic analysis of both plasma and urine, we identified ten overlapping proteins that significantly differentiate both time and dose variables. These shared plasma and urine proteins represent optimal candidate biomarkers of radiation exposure.

急性放射病（Acute radiation syndrome, ARS）是一类因全身暴露于高剂量辐射而引发的复杂多器官疾病。个体可通过多种途径遭遇全身辐射照射（total body irradiation, TBI），例如恐怖主义放射武器袭击或核事故。为明确个体是否暴露于高剂量辐射并需接受辐射干预治疗，亟需稳健的生物标志物（biomarker）以通过血液、尿液等生物样本估算辐射暴露剂量。为鉴定此类辐射暴露候选生物标志物（candidate biomarker），本研究采用高分辨率蛋白质组学（proteomics）技术，对接受全身辐射照射的非人灵长类动物（non-human primates）的血浆样本进行分析，照射源为钴-60（Co-60），照射剂量分别为6.7 Gy与7.4 Gy，观测周期为12天。本次血浆蛋白质组（plasma proteome）分析共评估了663种蛋白质，最终鉴定出一组具有特征性时间与剂量依赖性变化的血浆蛋白。除本次报道的血浆蛋白质组学研究外，我们近期还利用上述同一批非人灵长类动物的尿液样本完成了候选生物标志物的鉴定工作。通过对血浆与尿液的蛋白质组学分析，我们共鉴定出10种重叠蛋白质，这些蛋白质可显著区分时间与剂量两个变量。这些同时存在于血浆与尿液中的蛋白质，可作为辐射暴露的最优候选生物标志物。