Zaffaroni N, Orlandi L, Villa R, Bearzatto A, Rofstad E K, Silvestrini R
Istituto Nazionale per lo Studio e la Cura dei Tumori, Oncologia, Sperimentale C, Milan, Italy.
Int J Radiat Biol. 1994 Sep;66(3):279-85. doi: 10.1080/09553009414551211.
The accumulation and repair of radiation-induced DNA double-strand breaks (dsbs) were determined by neutral filter elution on 20 primary cultures obtained from ovarian cancer and malignant melanoma clinical specimens. The initial frequency of DNA dsbs after exposure to 50 Gy gamma-irradiation varied greatly for the individual cultures. However, melanomas were generally more efficient than ovarian cancers in repairing these DNA lesions (mean percentage of DNA dsb rejoined after 2 h: 83 versus 62%). In 13 of 20 cultures radiosensitivity was also assessed by the Courtenay clonogenic assay. The mean +/- SD of the surviving fraction at 2 Gy (SF2) was slightly higher for melanomas (0.56 +/- 0.25) than for ovarian carcinomas (0.43 +/- 0.23). No correlation was observed between SF2 and in vitro plating efficiencies or any biological characteristics of the tumour cell population, such as proliferative activity and DNA ploidy. Similarly, we failed to find any relation between the initial frequencies of DNA dsbs and SF2 in individual tumours. In contrast, a significant and direct relationship (r = 0.86, p < 0.01) was observed between SF2 and the percentages of DNA dsbs rejoined 2 h after irradiation. In agreement with reported data on human tumour established cell lines, our results indicate that the ability to repair DNA dsbs is an important determinant for radiation response even in primary cultures of clinical tumours.
通过中性滤膜洗脱法，对取自卵巢癌和恶性黑色素瘤临床标本的20种原代培养物进行检测，以确定辐射诱导的DNA双链断裂（dsbs）的积累和修复情况。暴露于50 Gy γ射线照射后，各培养物中DNA双链断裂的初始频率差异很大。然而，黑色素瘤在修复这些DNA损伤方面通常比卵巢癌更有效（照射2小时后DNA双链断裂重新连接的平均百分比：83%对62%）。在20种培养物中的13种中，还通过考特尼克隆形成试验评估了放射敏感性。黑色素瘤在2 Gy时的存活分数（SF2）的平均值±标准差（0.56±0.25）略高于卵巢癌（0.43±0.23）。未观察到SF2与体外接种效率或肿瘤细胞群体的任何生物学特征（如增殖活性和DNA倍性）之间存在相关性。同样，我们也未发现单个肿瘤中DNA双链断裂的初始频率与SF2之间存在任何关系。相反，观察到SF2与照射后2小时重新连接的DNA双链断裂百分比之间存在显著的直接关系（r = 0.86，p < 0.01）。与关于人类肿瘤建系细胞系的报道数据一致，我们的结果表明，即使在临床肿瘤的原代培养物中，修复DNA双链断裂的能力也是辐射反应的一个重要决定因素。
