Detection and repair of DNA base damages produced by ionizing radiation.
Detection and repair of DNA base damages produced by ionizing radiation.
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电离辐射产生的 DNA 碱基损伤的检测和修复。
DOI：
10.1002/em.2860050514
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Wallace,SS
中科院分区：
文献类型：
--
作者：
Wallace,SS
电离辐射是一种普遍存在的环境危害。为了能够评估诊断、治疗或职业辐射源照射的风险/效益比，必须能够评估辐射损害的生物后果。电离辐射在DNA中产生多种效应，包括单链和双链断裂、碱不稳定损伤、DNA-DNA和DNA-蛋白质交联，以及对嘌呤和嘧啶碱基以及脱氧核糖糖的损伤[综述参见Ward，19751。确定这些类别的主要标准一直是用来量化损害的具体衡量标准。基底损伤是产生的主要损伤[综述见Cerutti，19761]，此外还包括在上述其他类别中。也就是说，碱不稳定损害可能是由碱、糖或两者的损害引起的。单链或双链断裂可以邻近受损的糖或碱基。因此，上述大类可进一步细分为几类，这些类别可根据与之相关的特定碱基或糖损伤来区分。大量文献已确定电离辐射是致命的、诱变的和致癌的;但是，在此情况下，评估电离辐射引起的特定DNA损伤的生物学后果是极其困难的，因为在生物学上有意义的剂量下，相对于其它损伤的背景，以低产量产生损伤。这个问题是复杂的事实，非常少的测定可用于定量特定的基础损害。我们的方法来解决这个问题已经开发的方法来定量特定的病变，并评估其生物学后果，通过测量噬菌体噬菌体的生物活性。此外，我们已经从生物体中分离出了识别特异性DNA损伤的酶，这些生物体在遗传上具有很好的特征，因此我们最终可以将基因分配给分离的酶产物，并评估其在体内修复过程中的作用。
Ionizing radiation is a ubiquitous environmental hazard. In order to be able to evaluate the risWbenefit ratio of exposure from diagnostic, therapeutic, or occupational sources of radiation, it is essential to be able to assess the biological consequences of radiation damage. Ionizing radiation produces a variety of effects in DNA including single and double strand breaks, alkali labile lesions, both DNA-DNA and DNA-protein crosslink, as well as damages to the purine and pyrimidine bases and deoxyribose sugars [for review see Ward, 19751. The primary criterion for establishing these categories has been the particular measurement used to quantitate the damage. Base damages are the preponderant lesion produced [for a review see Cerutti, 19761 and are in addition included in the other above mentioned categories. That is, an alkali labile damage can result from damage to a base, sugar, or both. A single or double strand break can be adjacent to a damaged sugar or base. Thus, the broad categories described above can be further subdivided into classes which can be differentiated by the particular base or sugar lesion associated with it. A large body of literature has established that ionizing radiation is lethal, mutagenic, and carcinogenic; however, the assessment of the biological consequences of particular DNA lesions produced by ionizing radiation is extremely difficult because at biologically significant doses each unique damage is produced in low yields against a background of the other lesions. This problem is compounded by the fact that very few assays are available for quantitating particular base damages. Our approach to this problem has been to develop methods to quantitate particular lesions and to assess their biological consequences by measuring the biological activity of phage transfecting DNA. Further, we have isolated enzymes that recognize specific DNA damages from organisms that are well characterized genetically so that we can ultimately assign a gene to the enzyme product isolated and evaluate its role in in vivo repair processes.
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