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ELECTRON MIGRATION IN IRRADIATED DNA--AN EPR STUDY

辐照 DNA 中的电子迁移——一项 EPR 研究

基本信息

批准号：
2012341
负责人：
ABBAS PEZESHK
金额：
$ 10.4万
依托单位：
MINNESOTA STATE UNIVERSITY MOORHEAD
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-08-01 至 2001-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2012341
关键词：
DNA DNA damage bleomycin doxorubicin electron spin resonance spectroscopy electron transport gamma radiation gel electrophoresis intermolecular interaction plasmids radiation genetics

项目摘要

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.

描述：该项目的目标是了解电离辐射条件下 DNA 损伤的机制使用 EPR 光谱和链断裂相结合的方法进行直接损伤分析。计划进行实验研究来调查相互作用一系列抗肿瘤药物和 DNA 之间的关系。调查员建议研究以下药物： (a) 与 DNA 共价结合的药物，例如博来霉素，(b)小沟结合药物，例如偏端霉素，和(c) 嵌入剂，例如阿霉素。这项研究的一个主要目的是确定 DNA 和药物 DNA 中初级和次级自由基形成的程度 EPR 可检测到的 77K 系统将导致链断裂将其与伯自由基的产率联系起来。也有计划使用所提出的药物研究 DNA 中的电子迁移现象，并确定喷射电子相对于 DNA 的移动距离框架，在被困之前。简而言之，该方法是孵化将药物与水性 DNA（小牛胸腺）混合，然后将复合物冷冻至 77 K。 DNA 样本将受到 77K 的 g 射线照射，EPR 光谱将在液氦温度和需氧和厌氧条件下进行测量状况。在可比条件下进行平行实验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）可以保护细胞或使辐射损伤敏感系统，这将有助于癌症治疗。