Development of a minimally invasive biomarker assay to detect delayed radiation injury

项目摘要/摘要 由于核战争，普通民众继续面临暴露在电离辐射中的风险， 恐怖主义，或放射性事故。针对急性辐射综合征(ARS)的一些应对措施 被放置在国家储备中，增加了在辐射紧急情况下存活的机会。然而，个人 在ARS中幸存下来的人可能会在几个月到几年内发展出急性辐射暴露(DEARE)的延迟效应 照射后。目前，尚无系统可用于早期识别有感染风险的个人。 以及在哪些特定的器官系统中会发生晚期辐射损伤。因此，要使 辐射受害者的临床治疗，需要研究开发预测辐射受害者的微创分析方法 器官特异性死亡。然而，尽管约25%的总人口是儿科，但据我们所知，没有 已经在接触过艾滋病的受害者身上进行了Deare的预测性生物标记物分析研究 年纪还小。NIAID资助的U01 AI148308基金的主要目标是开发一种微创 生物标记物检测迟发性辐射损伤“是建立尿液和血浆辐射生物标记物检测方法。 有可能对主要器官系统造成损伤。在这个母项目中，尿液和血浆生物标记物的初步鉴定 在成年男性和女性中进行基于非靶向高分辨率质谱学的代谢组学研究 WAG/RijCmcr大鼠(11-12周龄)接受X射线(0、6、9.5和13Gy射线)照射，其中一只后腿受到 辐射以确保动物的长期生存。本补充申请的目的是扩大 通过确定幼年大鼠肺、肾和心脏损伤的早期生物标志物来确定父母资助的范围 模型，其中雄性和雌性大鼠暴露于41-44日龄的断腿X射线PBI。我们将使用 与亲本U01相同的大鼠品系和代谢组学/脂质组学方法，这将使我们能够 幼年大鼠与成年大鼠生物标志物面板的比较。

PROJECT SUMMARY/ABSTRACT The general population continues to be at risk of exposure to ionizing radiation because of nuclear warfare, terrorism, or radiological accidents. Some countermeasures of the acute radiation syndrome (ARS) have been placed in the national stockpile, increasing the chance of survival in a radiation emergency. However, individuals who survive the ARS may develop delayed effects of acute radiation exposure (DEARE) within months to years after irradiation. Currently, no system is available for the early identification of individuals who are at risk for DEARE and in which particular organ systems late radiation injuries will occur. Therefore, to personalize the clinical management of radiation victims, research is required to develop minimally invasive assays that predict organ-specific DEARE. However, although ~25% of the total population is pediatric, to our knowledge, no research has been performed in predictive biomarker assays of DEARE in victims who have been exposed at a young age. The main goal of the NIAID funded grant U01 AI148308 “Development of a minimally invasive biomarker assay to detect delayed radiation injury” is to develop urine and plasma biomarker assays of radiation injury to major organ systems at risk. In this parent project, the initial identification of urine and plasma biomarkers is performed with untargeted high-resolution mass spectrometry-based metabolomics in adult male and female WAG/RijCmcr rats (11-12 weeks of age) exposed to X-rays (0, 6, 9.5 and 13 Gy) with one hind-leg shielded from radiation to assure long-term survival of the animals. The purpose of this supplement application is to expand the scope of the parent grant by identifying early biomarkers of lung, kidney and heart injury in a juvenile rat model, in which male and female rats are exposed to leg-out X-ray PBI at the age of 41-44 days. We will use the same rat strain and metabolomics/lipidomics approaches as in the parent U01, which will enable us to make comparisons of biomarker panels in juvenile and adult rats.