EFFECTS OF RADIATIONS OF DIFFERENT QUALITIES ON CELLS - MOLECULAR MECHANISMS OF DAMAGE AND REPAIR
EFFECTS OF RADIATIONS OF DIFFERENT QUALITIES ON CELLS - MOLECULAR MECHANISMS OF DAMAGE AND REPAIR
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DOI：
10.1080/09553009314450721
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发表时间：
1993-05-01
影响因子：
2.6
通讯作者：
COX, R
中科院分区：
文献类型：
--
作者：
GOODHEAD, DT;THACKER, J;COX, R
讨论了不同质量的电离辐射的研究，特别强调对哺乳动物细胞DNA的损伤。以下是三个相关的主题。首先，超软X射线和慢重离子的失活和突变实验，加上辐射轨道结构的理论分析，强调了纳米尺度上局部轨道特征的生物学重要性。这导致的建议，轨道的关键物理特征是电离的随机聚类，直接在或非常接近DNA，导致成簇的初始分子损伤，包括各种组合的断裂，碱基损伤，交联等。定量的假设意味着，最终的细胞影响，从高LET辐射占主导地位的更严重的，因此较少的可修复的，集群的损害，这些是从占主导地位的低LET损害的性质不同。第二，不同类型辐射的相对有效性导致对染色体交换诱导机制的质疑。超软X射线的高效率，尽管它们的轨道长度很短，表明DNA损伤的单个位点可能通过涉及与未损伤DNA相互作用的分子过程导致交换。此外，它表明，一个单一的位点特异性DNA断裂，引入限制性内切酶，有时会导致一个大的缺失时，细胞提取物的错误修复。这些缺失发生在短的DNA重复序列之间，因此是一种“非法”重组的形式，但显然不涉及两个损伤位点的相互作用。第三，研究表明，来自辐射敏感性疾病共济失调-毛细血管扩张症（AT）患者的细胞缺乏辐射后恢复过程。AT细胞对高LET辐射的敏感性被发现相对于正常细胞降低，加强了高LET损伤不容易修复的概念。AT患者易于发生淋巴网状细胞癌，并且他们的细胞显示出特征性的染色体重排，这可能与特定基因组序列的错误修复有关。同样，对辐射诱发的小鼠白血病的研究表明，在富含端粒样重复序列的特定间质染色体位点发生了重排。
Studies of ionizing radiations of different quality are discussed with particular emphasis on damage to DNA of mammalian cells. Three related themes are followed. Firstly, inactivation and mutation experiments with ultrasoft X-rays and slow heavy ions, coupled with theoretical analyses of the structures of the radiation tracks, have emphasized the biological importance of localized track features over nanometre dimensions. This led to the suggestion that the critical physical features of the tracks are the stochastic clusterings of ionizations, directly in or very near to DNA, resulting in clustered initial molecular damage including various combinations of breaks, base damages, cross-links, etc. in the DNA. The quantitative hypotheses imply that final cellular effects from high-LET radiations are dominated by their more severe, and therefore less repairable, clustered damage, and that these are qualitatively different from the dominant low-LET damage. Second, relative effectiveness of different types of radiation led to questions on the mechanisms of induction of chromosome exchanges. The high efficiency of ultrasoft X-rays, despite their very short track lengths, suggested that single sites of DNA damage may lead to exchanges by a molecular process involving interaction with undamaged DNA. Also it is shown that a single site-specific DNA break, introduced by restriction enzymes, sometimes leads to a large deletion when misrepaired by cell extracts. These deletions occur between short DNA repeats, and are therefore a form of 'illegitimate' recombination, but clearly do not involve the interaction of two damage sites. Third, it was shown that cells from patients with the radiosensitive disorder ataxia-telangiectasia (AT) lack a post-irradiation recovery process. The sensitivity of AT cells to high LET radiations was found to be reduced relative to that for normal cells, reinforcing the concept that high LET damage is less easy to repair. AT patients are prone to lymphoreticular cancers, and their cells show characteristic chromosomal rearrangements, which may be associated with misrepair at specific genomic sequences. Similarly, studies of radiation-induced leukaemia in the mouse have implicated rearrangement at specific interstitial chromosome sites, which are rich in telomere-like repeat sequences.