ELECTRON MIGRATION IN IRRADIATED DNA--AN EPR STUDY

描述：本项目的目标是了解 电离辐射对DNA损伤的机制 EPR波谱与断链相结合的直接损伤研究 分析。计划进行实验研究来研究这种相互作用 一系列抗肿瘤药物和DNA之间的关系。调查员提议 研究下列药物：(A)与DNA共价结合的药物，如 博莱霉素，(B)小沟槽结合药物，如地塞霉素，和(C) 阿霉素等嵌入剂。这项研究的一个主要目的是确定 在DNA和药物DNA中形成的初级和次级自由基的程度 在77K下，EPR可检测到的系统将导致链断裂和 这与初级自由基的产率有关。还有一些计划 使用建议的药物研究DNA中的电子迁移现象， 并确定抛射出的电子相对于DNA的距离 在被困住之前，先把它框起来。简而言之，方法是孵化 药物与DNA水溶液(小牛胸腺)，然后将该复合体冷冻至77K。 DNA样品将在77K用g-射线照射，EPR谱将 在液氦温度、有氧和厌氧条件下进行测量 条件。平行实验，在可比较的条件下，也是 计划研究链断裂，使用凝胶电泳技术和 质粒DNA。该项目的长期目标是设计分子 (药物)能保护或敏化细胞辐射损伤的 系统，这将在癌症治疗中有用。

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.