A radiological/nuclear (RAD-NUC) incident, especially in an urban setting, results in diverse radiation-induced injuries due to heterogeneities in dose, the extent of partial-body shielding, human biodiversity and pre-existing health conditions. For example, acute radiation syndrome (ARS) can result in death within days to weeks of exposure to 0.7–10 Gy doses and is associated with destruction of the bone marrow, known as hematopoietic ARS (H-ARS). However, partial-body shielding that spares a portion of the bone marrow from exposure can significantly reduce the occurrence of H-ARS, but delayed effects of acute radiation exposure (DEARE) can still occur within months or years after exposure depending on the individual. In a mass casualty event, ideal triage must be able to pre-symptomatically identify individuals likely to develop radiation-induced injuries and provide an appropriate treatment plan. Today, while there are FDA approved treatments for hematopoietic ARS, there are no approved diagnosis for radiation injury and no approved treatments for the broad spectra of injuries associated with radiation. This has resulted in a major capability gap in the nations preparedness to a potentially catastrophic RAD-NUC event. Circulating microRNA (miRNA) are a promising class of biomarkers for this application because the molecules are accessible via a routine blood draw and are excreted by various tissues throughout the body. To test if miRNA can be used to predict distinct tissue-specific radiation-induced injuries, we compared the changes to the circulating miRNA profiles after total-body irradiation (TBI) and whole thorax lung irradiation (WTLI) in non-human primates at doses designed to induce ARS (day 2 postirradiation; 2–6.5 Gy) and DEARE (day 15 postirradiation; 9.8 or 10.7 Gy), respectively. In both models, miRNA sequences were identified that correlated with the onset of severe neutropenia (counts <500 µL^–1; TBI) or survival (WTLI). This method identified panels of eleven miRNA for both model and assigned functional roles for the panel members using gene ontology enrichment analysis. A common signature of radiation-induced injury was observed in both models: apoptosis, DNA damage repair, p53 signaling, pro-inflammatory response, and growth factor/cytokine signaling pathways were predicted to be disrupted. In addition, injury-specific pathways were identified. In TBI, pathways associated with ubiquitination, specifically of histone H2A, were enriched, suggesting more impact to DNA damage repair mechanisms and apoptosis. In WTLI, pro-fibrotic pathways including transforming growth factor (TGF-β) and bone morphogenetic protein (BMP) signaling pathways were enriched, consistent with the onset of late lung injury. These results suggest that miRNA may indeed be able to predict the onset of distinct types of radiation-induced injuries.

放射性/核 (RAD-NUC) 事件，尤其是在城市环境中，由于剂量的异质性、部分身体屏蔽的程度、人类生物多样性和预先存在的健康状况，会导致多种辐射引起的伤害。例如，急性辐射综合征 (ARS) 可在暴露于 0.7-10 Gy 剂量后数天至数周内导致死亡，并与骨髓破坏有关，称为造血 ARS (H-ARS)。然而，使部分骨髓免于暴露的局部身体屏蔽可以显着减少 H-ARS 的发生，但急性辐射暴露 (DEARE) 的延迟效应仍可能在暴露后数月或数年内发生，具体取决于个人。在大规模伤亡事件中，理想的分类必须能够在出现症状前识别出可能发生放射损伤的个体并提供适当的治疗计划。今天，虽然有 FDA 批准的造血 ARS 治疗方法，但没有批准的放射损伤诊断方法，也没有批准治疗与辐射相关的广泛损伤。这导致各国在应对潜在的灾难性 RAD-NUC 事件的准备方面存在重大能力差距。循环 microRNA (miRNA) 是用于该应用的一类很有前途的生物标志物，因为这些分子可通过常规抽血获得，并由全身各种组织排泄。为了测试 miRNA 是否可用于预测不同的组织特异性辐射诱导的损伤，我们比较了非人灵长类动物全身照射 (TBI) 和全胸肺照射 (WTLI) 后循环 miRNA 谱的变化，剂量设计为诱导 ARS（照射后第 2 天；2-6.5 Gy）和 DEARE（第 2 天） 15 后照射；分别为 9.8 或 10.7 Gy)。在这两种模型中，miRNA 序列被确定为与严重中性粒细胞减少症（计数 <500 µL^–1; TBI）或生存（WTLI）。该方法使用基因本体富集分析为模型确定了 11 个 miRNA 的面板，并为面板成员分配了功能角色。在两种模型中都观察到了辐射诱导损伤的一个共同特征：预测细胞凋亡、DNA 损伤修复、p53 信号、促炎反应和生长因子/细胞因子信号通路被破坏。此外，还确定了损伤特异性途径。在 TBI 中，与泛素化相关的通路，特别是组蛋白 H2A，被丰富，表明对 DNA 损伤修复机制和细胞凋亡的影响更大。在 WTLI 中，包括转化生长因子 (TGF-β) 和骨形态发生蛋白 (BMP) 信号通路在内的促纤维化通路被丰富，与晚期肺损伤的发作一致。