INITIAL EVENTS IN THE CELLULAR EFFECTS OF IONIZING-RADIATIONS - CLUSTERED DAMAGE IN DNA
INITIAL EVENTS IN THE CELLULAR EFFECTS OF IONIZING-RADIATIONS - CLUSTERED DAMAGE IN DNA
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DOI：
10.1080/09553009414550021
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发表时间：
1994-01-01
影响因子：
2.6
通讯作者：
GOODHEAD, DT
中科院分区：
文献类型：
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作者：
GOODHEAD, DT
一般的相关性之间的详细的空间和时间性质的初始物理特征的辐射损伤和最终的生物后果的可能性。尽管一系列物理、化学和生物过程消除了绝大多数早期损害，但这些问题依然存在。初始条件的详细信息应能为最相关的早期生物损伤和后续修复的关键特征提供指导。电离辐射在DNA中产生了数百种不同的简单化学产物，也产生了许多可能的聚集组合。简单的产物，包括单链断裂，往往与生物有效性相关性很差。即使对于最初的双链断裂，作为一个广泛的类别，有明显很少或没有增加的产量与电离密度增加，与细胞效应的相对生物学有效性的大幅上升。轨道结构分析表明，严重程度大于简单双链断裂的成簇DNA损伤很可能发生在所有电离辐射的生物相关频率。研究正在进行中，以更详细地描述这些簇状病变的化学性质，并考虑细胞修复的影响。据推测，更严重的例子的修复减少，并且主导最终细胞后果的病变谱严重偏向更严重的聚集组分。
General correlations are found between the detailed spatial and temporal nature of the initial physical features of radiation insult and the likelihood of final biological consequences. These persist despite the chain of physical, chemical and biological processes that eliminate the vast majority of the early damage. Details of the initial conditions should provide guidance to critical features of the most relevant early biological damage and subsequent repair. Ionizing radiations produce many hundreds of different simple chemical products in DNA and also multitudes of possible clustered combinations. The simple products, including single-strand breaks, tend to correlate poorly with biological effectiveness. Even for initial double-strand breaks, as a broad class, there is apparently little or no increase in yield with increasing ionization density, in contrast with the large rise in relative biological effectiveness for cellular effects. Track structure analysis has revealed that clustered DNA damage of severity greater than simple double-strand breaks is likely to occur at biologically relevant frequencies with all ionizing radiations. Studies are in progress to describe in more detail the chemical nature of these clustered lesions and to consider the implications for cellular repair. It has been hypothesized that there is reduced repair of the more severe examples and that the spectrum of lesions that dominate the final cellular consequences is heavily skewed towards the more severe, clustered components.