A standardized G2-assay for the prediction of individual radiosensitivity
A standardized G2-assay for the prediction of individual radiosensitivity
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DOI：
10.1016/j.radonc.2011.09.021
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发表时间：
2011-10-01
影响因子：
5.7
通讯作者：
Terzoudi, Georgia I.
中科院分区：
文献类型：
--
作者：
Pantelias, Gabriel E.;Terzoudi, Georgia I.
背景和目的：g2期辐照后染色单体断裂率的增加可能是对DNA损伤作出反应的放射敏感性易感基因的标志。我们已经证明了染色质-核蛋白复合物的动态特性，它能够快速展开、拆卸、组装和重折叠，影响辐射诱导的DNA损伤的修复，并在受损DNA位点的G2-M转换过程中导致染色单体断裂。在这里，我们研究了染色单体断裂的诱导和修复动力学，它们在放射敏感性易感性中的潜在作用，并提出了一种标准化的g2测定方法来评估个体放射敏感性。材料和方法：使用125名个体间放射敏感性差异显著的献血者（健康、癌症、at患者）的淋巴细胞，将g2检查点效率与染色单体断裂和个体放射敏感性联系起来。实验包括使用秋碱阻断和咖啡因治疗染色单体断裂的修复动力学，以废除g2检查点，产生内部控制并标准化g2测定。结果：在G2-M过渡期间，经过4小时的修复，辐射诱导的染色单体断裂保持不变，并且发现g2染色体放射敏感性与g2检查点效率之间存在显著相关性，以防止染色单体断裂。标准化的g2测定是通过对反映缺乏检查点和修复的条件引入标准化而开发的，类似于at患者的条件，为个体放射敏感性测试产生独特的标准。结论：标准化的g2测定可最大限度地减少实验室间和实验内的差异，并可直接应用于临床放疗方案的个体化。2011爱思唯尔爱尔兰有限公司版权所有。放射治疗与肿瘤学101 (2011)28-34
Background and purpose: An increased yield of chromatid breaks following G2-phase irradiation could be a marker of radiosensitivity-predisposing genes that respond to DNA damage. We have shown that the dynamic nature of chromatin-nucleoprotein complex, which is capable of rapid unfolding, disassembling, assembling and refolding, affects repair of radiation-induced DNA-lesions and causes chromatid breaks during G2-M transition in damaged DNA sites. Here, we investigate induction and repair kinetics of chromatid breaks, their potential role in radiosensitivity predisposition and a standardized G2-assay is proposed to assess individual radiosensitivity.Materials and methods: Lymphocytes from 125 blood donors with significant inter-individual radiosensitivity variation (healthy, cancer, AT-patients) are used to correlate G2-checkpoint efficiency with chromatid breakage and individual radiosensitivity. Experiments involve repair kinetics of chromatid breaks using colcemid-block and treatment with caffeine to abrogate G2-checkpoint, generate internal controls and standardize the G2-assay.Results: Radiation-induced chromatid breaks during G2-M transition, following 4 h repair, remained unchanged and a significant correlation between G2-chromosomal radiosensitivity and G2-checkpoint efficiency to prevent chromatid breakage was found. A standardized G2-assay is developed by introducing normalization to conditions reflecting lack of checkpoint and repair similar to those of AT-patients, generating a unique standard for individual radiosensitivity testing.Conclusions: The standardized G2-assay can minimize inter-laboratory and intra-experimental variations and may have straightforward application in clinical practice for individualization of radiotherapy protocols. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 101 (2011) 28-34