Initial radiation-induced DNA damage in human tumour cell lines: a correlation with intrinsic cellular radiosensitivity.

Initial radiation-induced DNA damage in human tumour cell lines: a correlation with intrinsic cellular radiosensitivity.
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DOI:
10.1038/bjc.1994.83
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发表时间:
1994-03
影响因子:
8.8
通讯作者:
Steel, G G
Steel, G G
中科院分区:
医学1区
文献类型:
--
作者:
Ruiz de Almodovar, J M;Nunez, M I;McMillan, T J;Olea, N;Mort, C;Villalobos, M;Pedraza, V;Steel, G G

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在人乳腺癌细胞和膀胱癌细胞系中,研究了初始DNA双链断裂(DSB)作为细胞放射敏感性决定因素的作用。用单层集落形成实验检测细胞存活率,观察放射敏感性的差异(α值在0.12到0.54之间)。经脉冲场凝胶电泳法(PFGE)后,剂量-效应曲线呈双相斜率,曲线平坦度在30GY以上。当使用基于DNA片段大小分布的数学模型评估DNADSB诱导频率时,我们发现DNADSB诱导的数量与相应的α值和2GY后存活的分数之间存在统计学上的显著关系(分别为P=0.0049和P=0.0031)。这些结果支持这样的观点,即初始损伤是细胞辐射敏感性的主要决定因素。
The role of the initial DNA double-strand breaks (dsb) as a determinant of cellular radiosensitivity was studied in human breast and bladder cancer cell lines. Cell survival was measured by monolayer colony-forming assay as appropriate and differences in radiosensitivity were seen (alpha-values ranged from 0.12 to 0.54). After pulsed-field gel electrophoresis (PFGE) the initial slopes of dose-response curves were biphasic with a flattening of the curves above 30 Gy. When the frequency of DNA dsb induction was assessed using a mathematical model based on the DNA fragment size distribution into the gel lane, we found a statistically significant relationship between the number of DNA dsb induced and the corresponding alpha-values and fraction surviving after 2Gy (P = 0.0049 and P = 0.0031 respectively). These results support the view that initial damage is a major determinant of cell radiosensitivity.