The Cellular Response to Complex DNA Damage Induced by Ionising Radiation.
The Cellular Response to Complex DNA Damage Induced by Ionising Radiation.
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DOI：
10.3390/ijms24054920
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发表时间：
2023-03-03
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
放射治疗(电离辐射；IR)用于治疗约50%的人类癌症，其中治疗效果主要是通过DNA损伤诱导实现的。特别是，复杂的DNA损伤(CDD)在DNA的一到两个螺旋转角内包含两个或多个损伤，是IR的标志，由于其难以通过细胞DNA修复机制进行修复，因此对细胞杀伤效应有很大贡献。CDD的水平和复杂性随着IR的电离密度(线性能量转移，LET)的增加而增加，因此光子(X射线)放射治疗被认为是低LET放射治疗，而一些粒子离子(如碳离子)被认为是高LET放射治疗。尽管有这些知识，但在细胞和组织中IR诱导的CDD的检测和定量测量方面仍存在挑战。此外，参与CDD修复的特定DNA修复蛋白和途径，包括DNA单链和双链断裂机制的组成部分，存在生物学上的不确定性，这在很大程度上取决于辐射类型和相关的LET。然而，有令人振奋的迹象表明，这些领域正在取得进展，这将加强我们对IR诱导的CDD细胞反应的理解。也有证据表明，靶向CDD修复，特别是通过针对选定的DNA修复酶的抑制剂，可以加剧更高LET的影响，这可以在翻译背景下进一步探索。
Radiotherapy (ionising radiation; IR) is utilised in the treatment of ~50% of all human cancers, and where the therapeutic effect is largely achieved through DNA damage induction. In particular, complex DNA damage (CDD) containing two or more lesions within one to two helical turns of the DNA is a signature of IR and contributes significantly to the cell killing effects due to the difficult nature of its repair by the cellular DNA repair machinery. The levels and complexity of CDD increase with increasing ionisation density (linear energy transfer, LET) of the IR, such that photon (X-ray) radiotherapy is deemed low-LET whereas some particle ions (such as carbon ions) are high-LET radiotherapy. Despite this knowledge, there are challenges in the detection and quantitative measurement of IR-induced CDD in cells and tissues. Furthermore, there are biological uncertainties with the specific DNA repair proteins and pathways, including components of DNA single and double strand break mechanisms, that are engaged in CDD repair, which very much depends on the radiation type and associated LET. However, there are promising signs that advancements are being made in these areas and which will enhance our understanding of the cellular response to CDD induced by IR. There is also evidence that targeting CDD repair, particularly through inhibitors against selected DNA repair enzymes, can exacerbate the impact of higher LET, which could be explored further in a translational context.
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影响因子：
3.4
作者：
Gerelchuluun A;Manabe E;Ishikawa T;Sun L;Itoh K;Sakae T;Suzuki K;Hirayama R;Asaithamby A;Chen DJ;Tsuboi K
通讯作者：
Tsuboi K
影响因子：
5.2
作者：
Görte J;Beyreuther E;Danen EHJ;Cordes N
通讯作者：
Cordes N
影响因子：
6.2
作者：
Delaney, G;Jacob, S;Barton, M
通讯作者：
Barton, M
影响因子：
3.5
作者：
Fenech M
通讯作者：
Fenech M
DOI：
10.1073/pnas.1016045108
发表时间：
2011-05-17
影响因子：
11.1
作者：
Asaithamby, Aroumougame;Hu, Burong;Chen, David J.
通讯作者：
Chen, David J.