THE COMPLEXITY OF DNA-DAMAGE - RELEVANCE TO BIOLOGICAL CONSEQUENCES
THE COMPLEXITY OF DNA-DAMAGE - RELEVANCE TO BIOLOGICAL CONSEQUENCES
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DOI：
10.1080/09553009414551401
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发表时间：
1994-11-01
影响因子：
2.6
通讯作者：
WARD, JF
中科院分区：
文献类型：
--
作者：
WARD, JF
当自由基迁移的范围受到羟基自由基清除剂的限制时（例如在细胞内），电离辐射会导致DNA中的单个和多个损伤位点。多重损伤位点被认为是更具有生物学相关性的，因为它们对细胞修复机制提出了挑战。这些位点以DNA双链断裂（dsb）的形式出现，但也可以作为其他多重损伤，在修复过程中可以转化为dsb。双链断裂的存在会导致碱基序列信息的丢失和/或允许断裂的两端分离并与错误的配偶体重新连接。（多重损伤部位也可能是由其他因素（如UVA、B和/或C光以及某些抗肿瘤抗生素）引起的生物学相关类型的损伤。）从DNA的辐射研究的定量数据显示，以支持拟议的机制，即通过清除和非清除机制，在细胞DNA中的复杂的损伤的生产。复杂损伤的产量反过来可以用来支持细胞突变是基因内这些损伤存在的结果的结论。文献数据被用来支持这些声明，并制定整体机制连接生产的主要物种的生产生物相关的损害。讨论了辐射LET对损伤多重性的影响，并对氧增强比随LET增大而减小的原因提出了建议。
Ionizing radiation causes both singly and multiply damaged sites in DNA when the range of radical migration is limited by the presence pf hydroxyl radical scavengers (e.g. within cells). Multiply damaged sites are considered to be more biologically relevant because of the challenges they present to cellular repair mechanisms. These sites occur in the form of DNA double-strand breaks (dsb) but also as other multiple damages that can be converted to dsb during attempted repair. The presence of a dsb can lead to loss of base sequence information and/or can permit the two ends of a break to separate and rejoin with the wrong partner. (Multiply damaged sites may also be the biologically relevant type of damage caused by other agents, such as UVA, B and/or C light, and some antitumour antibiotics.) The quantitative data available from radiation studies of DNA are shown to support the proposed mechanisms for the production of complex damage in cellular DNA, i.e. via scavengable and non-scavengable mechanisms. The yields of complex damages can in turn be used to support the conclusion that cellular mutations are a consequence of the presence of these damages within a gene. Literature data are used to support these statements and to develop overall mechanisms connecting the production of primary species to the production of biologically relevant damages. The consequences of the LET of the radiation on multiplicity of damage are discussed and suggestions made for the cause of the decrease of the oxygen enhancement ratio as the LET increases.