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低能电子诱导DNA损伤早期物理和化学事件的计算模型

Computational modelling of low-energy electron-induced DNA damage by early physical and chemical events.

作者信息

Nikjoo H, O'Neill P, Goodhead D T, Terrissol M

机构信息

MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire, U.K.

出版信息

Int J Radiat Biol. 1997 May;71(5):467-83. doi: 10.1080/095530097143798.

DOI:10.1080/095530097143798
PMID:9191891
Abstract

Modelling and calculations are presented as a first step towards mechanistic interpretation and prediction of radiation effects based on the spectrum of initial DNA damage produced by low energy electrons (100 eV-4.5 keV) that can be compared with experimental information. Relative yields of single and clustered strand breaks are presented in terms of complexity and source of damage, either by direct energy deposition or by reaction of OH radicals, and dependence on the activation probability of OH radicals and the amount of energy required to give a single strand break (ssb). Data show that the majority of interactions in DNA do not lead to damage in the form of strand breaks and when they do occur, they are most frequently simple ssb. However, for double-strand breaks (dsb), a high proportion (approximately 30%) are of more complex forms, even without considering additional complexity from base damage. The greater contribution is from direct interactions in the DNA but reactions of OH radicals add substantially to this, both in terms of the total number of breaks and in increasing the complexity within a cluster. It has been shown that the lengths of damaged segments of DNA from individual electron tracks tend to be short, indicating that consequent deletion length (simply by loss of a fragment between nearby dsb) would be short, very seldom exceeding a few tens of base pairs.

摘要

作为基于低能电子(100 eV - 4.5 keV)产生的初始DNA损伤谱对辐射效应进行机理解释和预测的第一步,本文给出了模型和计算结果,这些结果可与实验信息进行比较。单链断裂和簇状链断裂的相对产率根据损伤的复杂性和来源进行了阐述,损伤来源包括直接能量沉积或OH自由基反应,并依赖于OH自由基的活化概率以及产生一个单链断裂(ssb)所需的能量。数据表明,DNA中的大多数相互作用不会导致链断裂形式的损伤,而当链断裂发生时,最常见的是简单的单链断裂。然而,对于双链断裂(dsb),即使不考虑碱基损伤带来的额外复杂性,很大一部分(约30%)也是更复杂的形式。更大的贡献来自于DNA中的直接相互作用,但OH自由基反应在断裂总数以及增加簇内复杂性方面都对其有显著贡献。研究表明,来自单个电子轨迹的DNA损伤片段长度往往较短,这表明由此产生的缺失长度(仅通过相邻双链断裂之间片段的丢失)会很短,很少超过几十对碱基。

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