Low dose-rate fibroblast radiosensitivity and the prediction of patient response to radiotherapy
Low dose-rate fibroblast radiosensitivity and the prediction of patient response to radiotherapy
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DOI：
10.1080/095530096145021
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发表时间：
1996-09-01
影响因子：
2.6
通讯作者：
Peacock, JH
中科院分区：
文献类型：
--
作者：
Burnet, NG;Wurm, R;Peacock, JH
在过去的几年里，个体癌症患者的细胞放射敏感性和正常组织对放射治疗的反应之间的关系引起了越来越多的关注。最近的研究表明，成纤维细胞敏感性和正常组织反应之间存在相关性。我们研究了从四个正常个体和三个患者的皮肤活检中生长的成纤维细胞的放射敏感性，这些患者被确定为对临床放射治疗有意外的严重反应，这里称为“过度反应者”（OR）患者。在高剂量率（HDR）和低剂量率（LDR）照射后测量克隆形成存活率。通过比较两者，推导出LDR恢复因子。在4种细胞株中检测了潜在致死性损伤修复。HDR后，OR菌株与正常菌株无法区分。在LDR时，灵敏度范围扩大。OR菌株落在范围的敏感端，其特征在于缺乏LDR回收率，这清楚地将其与正常菌株区分开来。通过将所有数据集放在一起考虑而不是单独查看每个实验来估计实验误差。对来自几名患者的重复菌株进行了检测，发现它们之间的差异在估计的实验误差范围内，表明这些差异不具有生物学意义。这些数据与正常组织反应与个体细胞放射敏感性相关的假设一致。我们的数据证实了在细胞敏感性的临床研究中使用LDR照射的重要性。
The relationship between cellular radiosensitivity and normal-tissue response to radiotherapy in individual cancer patients has attracted increasing attention over the last few years. Recent work has suggested that a correlation exists between fibroblast sensitivity and normal-tissue reactions. We have examined the radiosensitivity of fibroblasts grown from skin biopsies of four normal individuals and three patients identified as having suffered unexpectedly severe reactions to clinical radiotherapy, called here 'over-reactor' (OR) patients. Clonogenic survival was measured after high (HDR) and low dose-rate (LDR) irradiation. By comparing the two, an LDR Recovery Factor was derived. Potentially-lethal damage repair was examined in 4 cell strains. After HDR the OR strains were indistinguishable from the normals. At LDR the range of sensitivity was expanded. The OR strains fell at the sensitive end of the range and were characterized by a lack of LDR recovery, which clearly distinguished them from the normal strains. Experimental errors were estimated by considering all the data sets together rather than viewing each experiment individually. Duplicate strains from several patients were tested, and the differences between them were found to be within the estimated experimental errors, suggesting that these differences were not biologically significant. The data are consistent with the hypothesis that normal-tissue response is linked to individual cellular radiosensitivity. Our data confirm the importance of using LDR irradiation in clinical investigations of cellular sensitivity.