IN VIVO DETECTION OF RADIATION INDUCED FREE RADICALS

描述：长期以来，人们一直认为，主要的有毒产品 电离辐射的主要成分是羟基自由基。它短暂的寿命 这使得它极难测量。然而，申请者已经 最近测量到的辐射诱导的羟基自由基直接在 利用他们开发的一项新技术，实时检测小鼠腿部肿瘤 实验室。羟基自由基是在它进化的部位检测到的 用一种新的甚低频电子顺磁共振(EPR) 光谱学与新的、强大的活体自旋捕捉相结合 技巧。这是一种非侵入性技术，不涉及损伤。 或破坏动物/病人的受试者。这些研究，尽管 初步的，最终将把自由基的进化与 电离辐射的生物效应。例如，这将允许 申请人预测辐射效应分量可以 通过清除羟基自由基来调节，并制定策略来 以最佳方式调节这些辐射效应。初始状态的条件 然而，测量结果是极端的。这项拨款申请的目的是 是进一步发展自旋/捕获/低频电子顺磁共振波谱 在临床上定位辐射所致的羟基自由基的形成 体内和实时细胞内、间质和组织中的辐射剂量 血管隔间。调查人员将使用这种技术来调查 进一步了解硫醇防护辐射损伤的基础知识 电离辐射对动物生物学效应的机制。

DESCRIPTION: It has long been believed that the predominant toxic product of ionizing radiation is the hydroxyl free radical. Its short lifetime makes it extremely difficult to measure. However, the applicants have recently measured radiation induced hydroxyl radical production directly in a murine leg tumor in real time, using a new technique developed in their laboratory. The hydroxyl radical was detected at the site where it evolved with a novel very low frequency electron paramagnetic resonance (EPR) spectroscopy in combination with new, robust in vivo spin trapping techniques. This is a noninvasive technique, which does not involve injury or destruction of the animal/patient subject. These studies, although preliminary, will eventually correlate the evolution of free radicals with the biologic effect of ionizing radiation. This, for example, will allow the applicants to predict that component of radiation effect that can be modulated by scavenging hydroxyl radicals and develop strategies to optimally modulate those radiation effects. The conditions of the initial measurement, however, were extreme. The objective of this grant application is to further develop spin/trapping/low frequency EPR spectroscopy to localize radiation induced hydroxyl radical formation at clinically relevant radiation doses in vivo and in real time in intracellular, interstitial and vascular compartments. The investigators will use this technique to probe thiol protection from radiation damage to further understand basic mechanisms of the biological effect of ionizing radiation in animals.