Wurm R, Burnet N G, Duggal N, Yarnold J R, Peacock J H
Radiotherapy Research Unit, Institute of Cancer Research, Sutton, Surrey, UK.
Int J Radiat Oncol Biol Phys. 1994 Oct 15;30(3):625-33. doi: 10.1016/0360-3016(92)90949-i.
To evaluate the relationship between radiation-induced cell survival and DNA damage in primary human fibroblasts to decide whether the initial or residual DNA damage levels are the more predictive of normal tissue cellular radiosensitivity.
Five primary human nonsyndromic and two primary ataxia telangiectasia fibroblast strains grown in monolayer were studied. Cell survival was assessed by clonogenic assay. Irradiation was given at high dose rate (HDR) 1-2 Gy/min. DNA damage was measured in stationary phase cells and expressed as fraction released from the well by pulsed-field gel electrophoresis (PFGE). For initial damage, cells were embedded in agarose and irradiated at HDR on ice. Residual DNA damage was measured in monolayer by allowing a 4-h repair period after HDR irradiation.
Following HDR irradiation, cell survival varied between SF2 0.025 to 0.23. Measurement of initial DNA damage demonstrated linear induction up to 30 Gy, with small differences in the slope of the dose-response curve between strains. No correlation between cell survival and initial damage was found. Residual damage increased linearly up to 80 Gy with a variation in slope by a factor of 3.2. Cell survival correlated with the slope of the dose-response curves for residual damage of the different strains (p = 0.003).
The relationship between radiation-induced cell survival and DNA damage in primary human fibroblasts of differing radiosensitivity is closest with the amount of DNA damage remaining after repair. If assays of DNA damage are to be used as predictors of normal tissue response to radiation, residual DNA damage provides the most likely correlation with cell survival.
评估原发性人成纤维细胞中辐射诱导的细胞存活与DNA损伤之间的关系，以确定初始或残留DNA损伤水平是否更能预测正常组织细胞的放射敏感性。
研究了五种原发性人非综合征和成纤维细胞以及两种原发性共济失调毛细血管扩张症成纤维细胞单层培养物。通过克隆形成试验评估细胞存活。以高剂量率（HDR）1-2 Gy/分钟进行照射。在静止期细胞中测量DNA损伤，并通过脉冲场凝胶电泳（PFGE）表示为从孔中释放的分数。对于初始损伤，将细胞包埋在琼脂糖中并在冰上以HDR照射。在HDR照射后允许4小时的修复期，在单层中测量残留DNA损伤。
HDR照射后，细胞存活在SF2为0.025至0.23之间变化。初始DNA损伤的测量显示，在30 Gy之前呈线性诱导，各菌株之间剂量反应曲线的斜率差异较小。未发现细胞存活与初始损伤之间的相关性。残留损伤在80 Gy之前呈线性增加，斜率变化系数为3.2。细胞存活与不同菌株残留损伤的剂量反应曲线斜率相关（p = 0.003）。
不同放射敏感性的原发性人成纤维细胞中辐射诱导的细胞存活与DNA损伤之间的关系与修复后残留的DNA损伤量最为密切。如果将DNA损伤检测用作正常组织对辐射反应的预测指标，残留DNA损伤与细胞存活最可能相关。
