Schwachöfer J H, Crooijmans R P, Hoogenhout H, Kal H B, Schaapveld R Q, Wessels J
Department of Radiotherapy, University Hospital, Nijmegen, The Netherlands.
Strahlenther Onkol. 1991 Jan;167(1):35-40.
We studied the relationship between the repair of radiation induced DNA strand breaks and cellular repair kinetics in two human tumor cell lines, NB-100 (neuroblastoma) and HN-1 (squamous cell carcinoma). Damage was quantified using the fluorometric analysis of DNA unwiding (FADU) for DNA damage, and cell survival was assessed using a clonogenic assay. In plateau phase cells repair of sublethal damage was virtually absent in NB-100 after 4 Gy (recovery ratio 1.0), whereas HN-1 cells did show sublethal damage repair (recovery ratio 1.4). Repair of potentially lethal damage was more pronounced in NB-100 cells (recovery ratio 2.3) than in HN-1 cells (recovery ratio 1.7) after 4 Gy. Graded doses of X-rays induced comparable levels of DNA damage in both tumor cell lines. However, in HN-1 cells more DNA strand breaks were repaired after 4 Gy, leaving about 25% of the initial damage unrepaired, whereas in NB-100 about 50% was unrepaired. This higher fraction of unrepaired DNA damage correlated well with the degree of sublethal damage repair which was lower in NB-100 than in HN-1 cell, but it did not correlate with the repair of potentially lethal damage, which was higher in NB-100 than in HN-1. Since the level of damage remaining post-irradiation may be the critical variable for survival, the FADU technique can contribute in elucidating the relationship between radiosensitivity and DNA damage repair capacity.
我们研究了两种人类肿瘤细胞系NB - 100(神经母细胞瘤)和HN - 1(鳞状细胞癌)中辐射诱导的DNA链断裂修复与细胞修复动力学之间的关系。使用DNA解旋荧光分析(FADU)对DNA损伤进行定量,并使用克隆形成试验评估细胞存活情况。在平台期细胞中,4 Gy照射后,NB - 100细胞几乎不存在亚致死损伤修复(恢复率为1.0),而HN - 1细胞确实表现出亚致死损伤修复(恢复率为1.4)。4 Gy照射后,NB - 100细胞(恢复率为2.3)的潜在致死损伤修复比HN - 1细胞(恢复率为1.7)更明显。不同剂量的X射线在两种肿瘤细胞系中诱导出相当水平的DNA损伤。然而,在4 Gy照射后,HN - 1细胞中更多的DNA链断裂得到修复,约25%的初始损伤未修复,而在NB - 100细胞中约50%未修复。未修复的DNA损伤的这一较高比例与亚致死损伤修复程度密切相关,NB - 100细胞中的亚致死损伤修复程度低于HN - 1细胞,但与潜在致死损伤的修复无关,NB - 100细胞中的潜在致死损伤修复高于HN - 1细胞。由于照射后剩余的损伤水平可能是生存的关键变量,FADU技术有助于阐明放射敏感性与DNA损伤修复能力之间的关系。