Foray Nicolas, Charvet Anne-Marie, Duchemin David, Favaudon Vincent, Lavalette Daniel
U647 INSERM-ID17-European Synchrotron Research Facility, 38043 Grenoble, France.
J Theor Biol. 2005 Oct 21;236(4):448-58. doi: 10.1016/j.jtbi.2005.03.027.
There is a large body of evidence that stress-induced DNA damage may be responsible for cell lethality, cancer proneness and/or immune reaction. However, statistical features of their repair rate remain poorly documented. In order to interpret the shape of the radiation-induced DNA damage repair curves with a minimum of biological assumptions, we introduced the concept of repair probability, specific to any individual radiation-induced DNA damage, whatever its biochemical type. We strengthened the apparent paradox that the repair rate of a population of DNA damage is time-dependent even if the repair rate of the individual DNA damage is constant. Hence, the existing models, based on a dual approach of the DNA repair may be insufficient for describing the DNA repair rate over a large range of repair times. Since the repair probability of DNA damage cannot be assessed individually, the measurement of the DNA repair rate is assumed to consist in determining the instantaneous mean of all repair probabilities. The relevance of this model was examined with different endpoints: cell species, genotypes, radiation type and chromatin condensation. The Euler's Gamma function was shown to provide the distribution the most consistent with such hypotheses. Furthermore, formulas, deduced from the Gamma distribution, were found to be compatible with our previous model, empirically defined but based on a variable repair half-time.
有大量证据表明，应激诱导的DNA损伤可能是细胞致死、癌症易感性和/或免疫反应的原因。然而，其修复率的统计特征仍缺乏充分记录。为了用最少的生物学假设来解释辐射诱导的DNA损伤修复曲线的形状，我们引入了修复概率的概念，该概念特定于任何个体辐射诱导的DNA损伤，无论其生化类型如何。我们强化了一个明显的悖论，即即使单个DNA损伤的修复率是恒定的，一群DNA损伤的修复率也是时间依赖性的。因此，基于DNA修复双重方法的现有模型可能不足以描述在大范围修复时间内的DNA修复率。由于无法单独评估DNA损伤的修复概率，因此假设DNA修复率的测量在于确定所有修复概率的瞬时平均值。用不同的终点来检验这个模型的相关性：细胞种类、基因型、辐射类型和染色质凝聚。结果表明，欧拉伽马函数提供了与这些假设最一致的分布。此外，从伽马分布推导出来的公式被发现与我们之前的模型兼容，之前的模型是根据经验定义的，但基于可变的修复半衰期。
