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首页> 外文期刊>International Journal of Radiation Biology: Covering the Physical, Chemical, Biological, and Medical Effects of Ionizing and Non-ionizing Radiations >Quantification of radiation induced DNA double-strand breaks in human fibroblasts by PFGE: testing the applicability of random breakage models.
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Quantification of radiation induced DNA double-strand breaks in human fibroblasts by PFGE: testing the applicability of random breakage models.

机译：通过PFGE对辐射诱导的人类成纤维细胞DNA双链断裂的定量：测试随机断裂模型的适用性。

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PURPOSE: To assess the applicability of methods of quantification of double-strand breaks (DSB) based on the random breakage paradigm, measuring yield and distribution of DSB induced by varying radiation quality. MATERIAL AND METHODS: 240 kVp X-rays and (238)Pu alpha-particles were used to induce DSB in AG01522B primary human fibroblasts. DNA molecular weight distributions were resolved by means of three pulsed-field gel-electrophoresis (PFGE) protocols, which, when combined together, allowed separation and quantification of double-stranded fragments between 5.7 Mbp and 12 kbp. Several analytical methods quantified the DSB yields. RESULTS: Data showed significant differences in the fragmentation patterns according to radiation quality. For both X-rays and alpha-particles, it was observed that the shape of the fragmentation profiles deviates from the prediction of a random breakage mechanism. This is in contrast to other studies where sparsely ionizing radiations appeared to distribute breaks uniformly throughout the genome. Deviations from random breakage were more evident after high linear energy transfer (LET) radiation, which showed an excess of breaks <1 Mbp and a deficit in the production of fragments >1 Mbp, a value that could be dose-dependent. CONCLUSIONS: Current methods of DNA fragmentation analysis after induction of DSB may lead to contradictory conclusions on both DSB yields and distributions. This study showed that the application of different DSB quantification methods, derived from random breakage or supported by its concepts, resulted in different radiation biological effectivenesses (RBE) for the induction of DSB, depending on how these methods were employed. To compare experimental results from different laboratories, care should be taken to provide as many details as possible about the application of methods of quantification of DNA damage. For all the methods used, total DSB yields resulted in RBE less than those for mutation induction or reproductive cell death, suggesting that total DSB yields only gave a limited indication of the severity of the inflicted damage. Production of correlated breaks on the chromatin loop structures by single particle-track traversals may explain the deviations observed between experimental data and the predictions of the random breakage paradigm.
机译：目的：评估基于随机断裂范式的双链断裂（DSB）定量方法的适用性，测量由不同辐射质量引起的DSB的产率和分布。材料与方法：使用240 kVp X射线和（238）Puα粒子在AG01522B初级人类成纤维细胞中诱导DSB。通过三种脉冲场凝胶电泳（PFGE）方案解析DNA分子量分布，将其组合在一起，可以分离和定量5.7 Mbp至12 kbp的双链片段。几种分析方法量化了DSB的产量。结果：数据显示，根据辐射质量，碎片模式存在显着差异。对于X射线和α粒子，均观察到碎片轮廓的形状偏离了随机断裂机理的预测。这与其他研究相反，在其他研究中，稀疏电离辐射似乎在整个基因组中均匀分布断裂。在高线性能量转移（LET）辐射后，与随机断裂的偏差更加明显，这表明断裂<1 Mbp时过量，片段产生> 1 Mbp时产生缺陷，该值可能与剂量有关。结论：诱导DSB后DNA片段分析的当前方法可能导致DSB产量和分布的结论相互矛盾。这项研究表明，源自随机断裂或受其概念支持的不同DSB定量方法的应用，导致了不同的辐射生物学效应（RBE）诱导DSB，具体取决于这些方法的使用方式。为了比较来自不同实验室的实验结果，应注意提供尽可能多的DNA损伤定量方法应用细节。对于所有使用的方法，DSB的总产量导致的RBE少于突变诱导或生殖细胞死亡的RBE，这表明DSB的总产量仅给出了造成损害的严重程度的有限指示。通过单粒子迹线遍历在染色质环结构上产生相关的断裂可以解释实验数据与随机断裂范例的预测之间观察到的偏差。

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