Schwartz J L, Mustafi R, Beckett M A, Weichselbaum R R
Department of Radiation and Cellular Oncology, University of Chicago, Illinois 60637.
Radiat Res. 1990 Jul;123(1):1-6.
Radioresistant tumor cells are found in tumor specimens from patients in whom radiotherapy has failed or whose tumors have recurred after therapy. This suggests that inherent cellular radioresistance may in part underlie the failure of radiotherapy, and therefore determination of the presence of resistant cells within a tumor might be a useful predictor of response to radiation therapy. Most standard clonogenic assays of radiation response are time-consuming, and alternative assays of radiation response are being sought. In an earlier publication (J. L. Schwartz et al., Int. J. Radiat. Oncol. Biol. Phys. 15, 907-912, 1988), we reported that radioresistant human tumor cells rejoin DNA double-strand breaks, as measured by DNA neutral filter elution (pH 9.6), faster than more sensitive cell lines. To determine whether DNA elution might have potential as a rapid predictive assay, we examined the relationship between the rate of DNA double-strand break rejoining and radiosensitivity in nine first-passage-after-explant squamous cell carcinomas under conditions that minimized the influence of nontumor and nonclonogenic cells. The frequency of DNA double-strand breaks measured 1 h after irradiation with 100 Gy 60Co gamma rays was used as an estimate of relative rejoining rate. This number is a reflection of both the initial DNA double-strand break frequency and the amount of repair that occurs in 1 h. The relative break frequency was compared to radiosensitivity as measured by standard clonogenic survival assays in later passages (p3-p14) of these same cells. A significant relationship (r = 0.61, P less than 0.01) was found between break frequency measured in first-passage cells and radiosensitivity measured in later passages, suggesting that the neutral elution assay as described here has some promise as a relatively rapid assay of the radiosensitivity of human tumor cells.
在放疗失败或治疗后肿瘤复发患者的肿瘤标本中发现了耐辐射肿瘤细胞。这表明内在的细胞辐射抗性可能部分是放疗失败的原因，因此确定肿瘤内抗性细胞的存在可能是放疗反应的一个有用预测指标。大多数标准的辐射反应克隆形成试验耗时较长，人们正在寻找替代的辐射反应试验方法。在早期的一篇出版物（J. L. Schwartz等人，《国际放射肿瘤学、生物学和物理学杂志》15，907 - 912，1988年）中，我们报道，通过DNA中性滤膜洗脱法（pH 9.6）测量，耐辐射的人肿瘤细胞比更敏感的细胞系更快地重新连接DNA双链断裂。为了确定DNA洗脱是否有可能作为一种快速预测试验，我们在尽量减少非肿瘤细胞和非克隆形成细胞影响的条件下，研究了9例原代培养后传代的鳞状细胞癌中DNA双链断裂重新连接速率与放射敏感性之间的关系。用100 Gy 60Coγ射线照射1小时后测量的DNA双链断裂频率作为相对重新连接速率的估计值。这个数字反映了初始DNA双链断裂频率和1小时内发生的修复量。将相对断裂频率与这些相同细胞后期传代（p3 - p14）时通过标准克隆形成存活试验测量的放射敏感性进行比较。在原代培养细胞中测量的断裂频率与后期传代中测量的放射敏感性之间发现了显著关系（r = 0.61，P < 0.01），这表明此处所述的中性洗脱试验作为一种相对快速的人肿瘤细胞放射敏感性试验有一定前景。
