Smeets M F, Mooren E H, Abdel-Wahab A H, Bartelink H, Begg A C
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam.
Radiat Res. 1994 Nov;140(2):153-60.
The goal of these experiments was to investigate further the relationship between DNA double-strand breaks and cell killing in human tumor cells, first by comparing different cell lines, and second by radiomodification studies. Field-inversion gel electrophoresis was used to quantify double-strand breaks. Two subclones of the radioresistant human squamous cell carcinoma line SQ20B (SQD9 and SQG6) were compared. These subclones differed in DNA index by a factor of 1.7 but showed the same resistance to radiation as cells of the parental cell line. It was found that, although induction of DSBs was not significantly different in the two cell lines, the t1/2 of the fast component of repair was significantly shorter for SQD9 cells, leading to greater overall repair which was not reflected in increased survival. Caffeine and cysteamine were tested as modifiers of radiosensitivity, using the radioresistant SQ20B line and the radiosensitive SCC61 cell line. No effect of caffeine was seen when the drug was present only during irradiation. Postirradiation incubations with caffeine, however, resulted in a dose reduction factor greater than 2.0 in cell survival for both cell lines. In contrast, induction of DSBs was reduced by caffeine, and no effect on DSB repair was observed. Cysteamine led to a dose protection factor greater than 1.8 in cell survival in both cell lines. A reduction in induced DSBs was found at high doses corresponding approximately with the increase in cell survival. Over the same (low) dose range, however, the correlation between DSB induction and cell killing was poor. These data indicate that DSB induction does not correlate well with cell killing either for different cell lines, for radiochemical modification (cysteamine) or for some other types of modification (caffeine).
这些实验的目的是进一步研究人类肿瘤细胞中DNA双链断裂与细胞杀伤之间的关系，首先是比较不同的细胞系，其次是进行放射修饰研究。采用脉冲场凝胶电泳来定量双链断裂。比较了耐辐射的人鳞状细胞癌系SQ20B的两个亚克隆（SQD9和SQG6）。这些亚克隆的DNA指数相差1.7倍，但对辐射的抗性与亲本细胞系的细胞相同。结果发现，虽然两个细胞系中双链断裂的诱导没有显著差异，但SQD9细胞修复的快速成分的t1/2明显更短，导致总体修复程度更高，但这并未反映在存活率的提高上。使用耐辐射的SQ20B细胞系和对辐射敏感的SCC61细胞系，测试了咖啡因和半胱胺作为放射敏感性的修饰剂。仅在照射期间存在该药物时，未观察到咖啡因有任何作用。然而，照射后用咖啡因孵育，两个细胞系的细胞存活率的剂量降低因子均大于2.0。相比之下，咖啡因可减少双链断裂的诱导，且未观察到对双链断裂修复有任何影响。半胱胺使两个细胞系的细胞存活率的剂量保护因子均大于1.8。在高剂量下发现诱导的双链断裂减少，这大致与细胞存活率的增加相对应。然而，在相同的（低）剂量范围内，双链断裂诱导与细胞杀伤之间的相关性较差。这些数据表明，无论是对于不同的细胞系、放射化学修饰（半胱胺）还是其他一些类型的修饰（咖啡因），双链断裂诱导与细胞杀伤之间的相关性都不佳。
