Affentranger M I, Burkart W
Paul Scherrer Institute, Radiation Hygiene, Villigen PSI, Switzerland.
J Histochem Cytochem. 1995 Feb;43(2):229-35. doi: 10.1177/43.2.7529787.
Both X-rays and the radiomimetic agent bleomycin (BLM) induce DNA strand breaks, predominantly via reactive radicals. To compare the induction of breaks with the two agents in Chinese hamster (CHO-K1) cells, two different alkaline unwinding methods, a 3H tracer-based analysis of large cell populations and an optical adaption allowing measurement of single cells, were applied. Radiation and BLM show qualitatively similar dose responses when the average number of DNA strand breaks is measured in a large cell population. However, the breakage pattern at the single-cell level indicates large discrepancies between the actions of the two agents. Irradiated cells show a uniform distribution of DNA strand breaks over the cell population. Effects of treatment with 30 micrograms x ml-1 BLM for 2 hr vary from practically zero in some cells to high levels of DNA strand breakage in others. Unlike the repair of radiation-induced DNA breaks, the repair efficiency of BLM-induced DNA strand breaks, as measured at the single-cell level, varies strongly among cells of the same population. Such heterogeneity at the cellular level potentially reduces BLM's usefulness for tumor therapy because the appearance of BLM-resistant subpopulations may critically impair treatment outcome.
X射线和拟放射剂博来霉素（BLM）都主要通过活性自由基诱导DNA链断裂。为了比较这两种试剂在中国仓鼠（CHO-K1）细胞中诱导断裂的情况，应用了两种不同的碱性解旋方法：一种基于3H示踪剂对大量细胞群体进行分析，另一种是通过光学适配来测量单个细胞。当在大量细胞群体中测量DNA链断裂的平均数时，辐射和BLM显示出定性相似的剂量反应。然而，单细胞水平的断裂模式表明这两种试剂的作用存在很大差异。受辐射的细胞在细胞群体中显示出DNA链断裂的均匀分布。用30微克/毫升的BLM处理2小时的效果在一些细胞中几乎为零，而在另一些细胞中则导致高水平的DNA链断裂。与辐射诱导的DNA断裂修复不同，在单细胞水平测量时，BLM诱导的DNA链断裂的修复效率在同一群体的细胞中差异很大。细胞水平的这种异质性可能会降低BLM在肿瘤治疗中的效用，因为对BLM耐药的亚群的出现可能会严重损害治疗效果。
