ELECTRON MIGRATION IN IRRADIATED DNA--AN EPR STUDY

描述：本项目的目标是了解 电离辐射条件下DNA损伤的机制 使用EPR光谱和链断裂的组合方法的直接损伤 分析. 实验研究计划调查的相互作用 一系列抗肿瘤药物和DNA之间的联系。 研究者建议 研究以下药物：（a）与DNA共价结合的药物， 博来霉素，（B）小沟结合药物如偏端霉素，和（c） 嵌入剂如阿霉素。 本研究的主要目的是确定 在DNA和药物DNA中形成的初级自由基和次级自由基的程度 EPR可检测到的77K系统将导致链断裂， 与初级自由基的产率相关。 还计划 使用所提出的药物研究DNA中的电子迁移现象， 并确定射出的电子相对于DNA的距离 在被困之前， 简单地说，方法是孵化 将药物与含水DNA（小牛胸腺）混合，然后将复合物冷冻至77 K。 DNA样品将在77K下用g射线辐照，EPR谱将 在液氦温度和有氧和厌氧条件下测量 条件 在可比条件下的平行实验也是 计划使用凝胶电泳技术研究链断裂， 质粒DNA。 该项目的长期目标是设计分子 （药物）可以保护或敏感辐射损伤细胞 系统，这将是有用的癌症治疗。

DESCRIPTION: The objective of this project is the understanding of mechanisms involved in DNA damage by ionizing radiation under conditions of direct damage using a combined approach of EPR spectroscopy and strand-break analysis. Experimental studies are planned to investigate the interaction between a range of antitumor drugs and DNA. The investigator proposes to study the following drugs: (a) drugs that covalently bind to DNA such as bleomycin, (b) minor groove binding drugs such as distamycin, and (c) intercalators such as adriamycin. A major aim of this study is to determine to what extent the primary and secondary radicals formed in DNA and drug-DNA systems at 77K, that are detectable by EPR, will lead to strand breaks and relate that to the yields of primary radicals. There are also plans to study the phenomenon of electron migration in DNA using the proposed drugs, and determine the distance the ejected electrons travel, relative to the DNA frame, before being trapped. Briefly, the methodology is to incubate the drugs with aqueous DNA (calf thymus) and then freeze the complex to 77 K. DNA samples will be irradiated with g-rays at 77K and the EPR spectra will be measured at liquid helium temperature and under aerobic and anaerobic conditions. Parallel experiments, under comparable conditions, are also planned to study strand-breaks, using the gel electrophoresis technique and plasmid DNA. The long-range goal of the project is to design molecules (drugs) that can either protect, or sensitize radiation damage to cellular systems, which would be useful in cancer therapy.