BIOCHEMISTRY AND RADIOPROTECTION FROM RADIATION CATARACT

辐射白内障的生物化学和放射防护

• 批准号: 3263870
• 负责人: JOHN C LIVESEY
• 金额: $ 13.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3263870
• 关键词: cataract; laboratory mouse; laboratory rat; linear energy transfer; radiation carcinogenesis; radiation dosage; radiation sensitivity; radioprotective agents

Our objective is to define the process of chemical protection from radiation-induced cataracts to further clarify the mechanisms of radiation cataract formation and the mechanisms of chemical radioprotection. Our ultimate goal is to develop a radioprotective drug with clinical utility. The formation of radiation cataracts involves both biochemical and histological changes in the lens of the affected eye which we will follow over time after radiation exposure. The addition of a drug substance which prevents the formation of cataracts should give valuable information on which parameters of lens biochemistry are important in the process of cataract formation, as we will be able to differentiate those factors whose alterations are coincident with eventual cataract formation. Conversely, biochemical alterations in irradiated lenses will give an early indication of lens pathology, allowing definition of those radiobiological factors which are necessary to develop a drug which protects against radiation cataracts. In preliminary studies, we have validated the concept of chemical protection by the radioprotective drug S-3-amino-2-hydroxypropyl-phorsphorothioic acid (WR-77913) against radiation cataracts. We propose studies of several parameters of lens biochemistry (phase transition temperature, protein precipitation, protein molecular weight distribution, and thiol redox status) which are known to be altered during cataract development. These studies will be performed on groups of animals which receive varying doses of either radioprotective drug or radiation. Dose-response relationships will be defined for these parameters which are important in lens radioprotection. Additionally, we will test the protective effect of WR-77913 against radiations of different quality (gamma rays and neutrons) and the effects of different radioprotective drugs (cysteamine, WR-2721 and their derivatives) on the biochemistry of radiation cataractogenesis.

我们的目标是定义化学防护过程， 辐射引起的白内障，以进一步阐明辐射的机制 白内障的形成和化学辐射防护的机制。 我们 最终目标是开发具有临床实用性的辐射防护药物。 辐射性白内障的形成涉及生物化学和 我们将跟踪观察患眼透镜的组织学变化 随着时间的推移辐射暴露后。 添加一种原料药， 预防白内障的形成应该提供有价值的信息， 透镜生物化学的哪些参数在 白内障形成，因为我们将能够区分这些因素， 改变与最终的白内障形成一致。 相反地， 受照射晶状体中的生化变化将给出早期指示 透镜病理学，允许定义这些放射生物学因素 这是开发抗辐射药物所必需的 白内障 在初步研究中，我们验证了 辐射防护药的化学防护 S-3-氨基-2-羟丙基-硫代磷酸（WR-77913） 辐射性白内障 我们提出了几个参数的研究透镜生化（相位 转变温度，蛋白质沉淀，蛋白质分子量 分布和硫醇氧化还原状态），已知这些变化在 白内障发展 这些研究将在动物组中进行 其接受不同剂量的辐射防护药物或辐射。 将为这些参数定义剂量-反应关系， 在透镜辐射防护中很重要。 此外，我们将测试 WR-77913对不同质量辐射的防护作用 （伽马射线和中子）和不同辐射防护剂的效果 药物（半胱胺，WR-2721及其衍生物）对生物化学 辐射性白内障