From DNA radiation damage to cell death: theoretical approaches.
From DNA radiation damage to cell death: theoretical approaches.
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DOI：
10.4061/2010/350608
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发表时间：
2010-10-05
影响因子：
2.3
通讯作者：
Ballarini F
中科院分区：
文献类型：
--
作者：
Ballarini F
辐射诱导细胞死亡是放射生物学研究的一个重要终点，本文综述了几种有代表性的辐射诱导细胞死亡模型。确定了基本假设，分析了它们对预测细胞存活的影响，并概述了每种方法的优点和缺点。除了靶理论、线性二次模型、双辐射作用理论和Katz模型等“历史”方法外，还讨论了最近的局部效应模型，重点讨论了它在碳离子强子治疗中的应用。此外，还介绍了帕维亚大学根据细胞失活与染色体畸变之间的关系开发的一个机理模型，以及最近的结果;不同辐射类型的模型预测和文献实验数据之间的良好协议（光子，质子，阿尔法粒子，和碳离子）支持这样的观点，即不对称染色体畸变如双着丝粒和环在细胞死亡中起着重要作用。基于这些结果，还提出了对Tlymphocyte的重新解释，将Tlymphocyte“亚病变”和“病变”分别确定为成簇的DNA双链断裂和（致死性）染色体畸变。
Some representative models of radiation-induced cell death, which is a crucial endpoint in radiobiology, were reviewed. The basic assumptions were identified, their consequences on predicted cell survival were analyzed, and the advantages and drawbacks of each approach were outlined. In addition to “historical” approaches such as the Target Theory, the Linear-Quadratic model, the Theory of Dual Radiation Action and Katz' model, the more recent Local Effect Model was discussed, focusing on its application in Carbon-ion hadrontherapy. Furthermore, a mechanistic model developed at the University of Pavia and based on the relationship between cell inactivation and chromosome aberrations was presented, together with recent results; the good agreement between model predictions and literature experimental data on different radiation types (photons, protons, alpha particles, and Carbon ions) supported the idea that asymmetric chromosome aberrations like dicentrics and rings play a fundamental role for cell death. Basing on these results, a reinterpretation of the TDRA was also proposed, identifying the TDRA “sublesions” and “lesions” as clustered DNA double-strand breaks and (lethal) chromosome aberrations, respectively.