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

项目总结/摘要 由于核战争，普通民众继续面临电离辐射的风险， 恐怖主义或放射性事故。介绍了急性放射综合征（ARS）的一些防治措施 储存在国家储备中，增加了在辐射紧急情况下的生存机会。然而，个人 在ARS中存活的患者可能在数月至数年内出现急性辐射暴露（DEARE）的延迟效应 照射后目前，没有系统可用于早期识别有风险的个人， 并在特定的器官系统中发生晚期辐射损伤。因此，要个性化 放射受害者的临床管理，需要研究开发微创检测， 器官特异性DEARE。然而，尽管总人口的~25%是儿科，据我们所知， 研究已经在DEARE的预测生物标志物测定中进行，这些生物标志物测定是在 年纪轻轻NIAID资助的赠款U 01 AI 148308的主要目标是“开发微创 检测迟发性辐射损伤的生物标志物测定”是发展放射性损伤的尿和血浆生物标志物测定 对主要器官系统的伤害有风险。在这个母项目中，尿液和血浆生物标志物的初步鉴定 在成年男性和女性中使用基于非靶向高分辨率质谱的代谢组学 WAG/RijCmcr大鼠（11-12周龄）暴露于X射线（0、6、9.5和13戈伊），一条后腿被屏蔽， 辐射，以确保动物的长期生存。这一补充申请的目的是扩大 通过识别幼年大鼠肺、肾和心脏损伤的早期生物标志物， 模型中，雄性和雌性大鼠在41-44日龄时暴露于腿外X射线PBI。我们将使用 与亲本U 01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 幼龄和成年大鼠中生物标志物组的比较。

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.