IN VIVO DETECTION OF RADIATION INDUCED FREE RADICALS

辐射诱发自由基的体内检测

• 批准号: 2414437
• 负责人: HOWARD J HALPERN
• 金额: $ 30.58万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2414437
• 关键词: adduct; biomedical equipment development; chemical stability; chemical synthesis; computer simulation; deuterium; electron spin resonance spectroscopy; free radical scavengers; hydroxyl radical; ionizing radiation; laboratory mouse; laboratory rat; method development; neoplasm /cancer transplantation; nitrone; pharmacokinetics; radiation dosage; radiation protection; radiobiology; radioprotective agents; reduction; thiols; tissue /cell culture; tritium

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.

描述：长期以来，人们一直认为， 是羟基自由基。 它短暂的寿命 使得它非常难以测量。 然而，申请人有 最近测得的辐射诱导的羟基自由基的生产直接在 一个小鼠腿部肿瘤在真实的时间，使用一种新的技术开发的，在他们的 实验室 羟基自由基是在它进化的地方被检测到的 用一种新的甚低频电子顺磁共振（EPR） 光谱学与新的、稳健的体内自旋捕获相结合 技术. 这是一种非侵入性技术，不涉及损伤 或破坏动物/患者受试者。 这些研究虽然 初步，最终将自由基的演变与 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， 通过清除羟基自由基进行调节，并制定策略， 最佳地调节这些辐射效应。 初始条件 然而，测量是极端的。 这项拨款申请的目的 进一步发展自旋/俘获/低频EPR光谱学， 将放射诱导的羟基自由基形成局限于临床相关 在体内和在细胞内、间质和细胞外的真实的时间内的辐射剂量 血管间室 调查人员将利用这种技术来探测 巯基保护免受辐射损伤，以进一步了解基本的 电离辐射对动物的生物效应的机制。