DNA DAMAGE CAUSED BY IONIZING-RADIATION
DNA DAMAGE CAUSED BY IONIZING-RADIATION
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DOI：
10.1016/0025-5564(92)90028-u
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发表时间：
1992-12-01
影响因子：
4.3
通讯作者：
HLATKY, LR
中科院分区：
文献类型：
--
作者：
SACHS, RK;CHEN, PL;HLATKY, LR
综述了电离辐射对哺乳动物细胞基因组损伤的连续时间马尔可夫链模型。在这类模型中，辐射引起的即时损伤被视为DNA双链断裂(DSB)的批量泊松到达过程。直接损伤的酶修饰被模拟为类似于随机化学动力学主方程所描述的马尔可夫过程。一个说明性的例子是归还/完全交换模型。该模型假设，在辐射诱导后，DSB随后要么经历酶介导的修复(修复)，要么参与成对的染色体交换。其中一些交换会造成不可修复的损害，如双着丝粒染色体异常。可以先进行快速照射，然后进行酶DSB处理，或者进行较长时间的照射，使DSB到达和酶DSB处理在整个照射期间继续进行。分析马尔可夫链的方法包括使用期望值的近似模型、嵌入在转变处的离散时间马尔可夫链、生成函数的偏微分方程式、正规摄动理论、具有标度的奇异摄动理论、数值计算，以及将Perron-Frobenius理论与变分估计相结合的某些矩阵方法。简要概述了DNA损伤的期望值、方差和统计分布的实验结果的应用。连续时间马尔可夫链是这些辐射损伤模型中最系统的，它将细胞核内的DSB-DSB相互作用视为同质(例如，忽略扩散限制)。它们实际上包含了所有其他相关的同质模型和半经验总结，作为特例、极限情况或近似。然而，马尔可夫模型似乎不太适合研究DSB相互作用的空间相关性，这在某些情况下是重要的。
A survey is given of continuous-time Markov chain models for ionizing radiation damage to the genome of mammalian cells. In such models, immediate damage induced by the radiation is regarded as a batch-Poisson arrival process of DNA double-strand breaks (DSBs). Enzymatic modification of the immediate damage is modeled as a Markov process similar to those described by the master equation of stochastic chemical kinetics. An illustrative example is the restitution/complete-exchange model. The model postulates that, after being induced by radiation, DSBs subsequently either undergo enzymatically mediated restitution (repair) or participate pairwise in chromosome exchanges. Some of the exchanges make irremediable lesions such as dicentric chromosome aberrations. One may have rapid irradiation followed by enzymatic DSB processing or have prolonged irradiation with both DSB arrival and enzymatic DSB processing continuing throughout the irradiation period. Methods for analyzing the Markov chains include using an approximate model for expected values, the discrete-time Markov chain embedded at transitions, partial differential equations for generating functions, normal perturbation theory, singular perturbation theory with scaling, numerical computations, and certain matrix methods that combine Perron-Frobenius theory with variational estimates. Applications to experimental results on expected values, variances, and statistical distributions of DNA lesions are briefly outlined. Continuous-time Markov chains are the most systematic of those radiation damage models that treat DSB-DSB interactions within the cell nucleus as homogeneous (e.g., ignore diffusion limitations). They contain virtually all other relevant homogeneous models and semiempirical summaries as special cases, limiting cases, or approximations. However, the Markov models do not seem to be well suited for studying spatial dependence of DSB interactions, which is known to be important in some situations.