Brock W A, Williams M, McNaney D, Milas L, Peters L J, Weichselbaum R R
Int J Radiat Oncol Biol Phys. 1984 Nov;10(11):2113-7. doi: 10.1016/0360-3016(84)90210-4.
Because of the potential clinical significance of the report that dexamethasone is a radioprotector of Chinese hamster V-79 cells, the effect of dexamethasone treatment on the radiosensitivity of five other cultured mammalian cell lines (including two human cell lines) was tested and preliminary investigations into the mechanism of protection of V-79 cells were undertaken. In agreement with the published results of others, we found that treatment of V-79 cells with dexamethasone results in a 1.3-fold increase in D0. Conversely, dexamethasone had no effect on the radiosensitivity of Chinese hamster ovary cells, murine fibrosarcoma, rat glioma cells, human diploid fibroblasts, or human mammary carcinoma cells. To study the mechanism of the radioprotective effect of dexamethasone on V-79 cells, the cell cycle was examined. Dexamethasone treatment causes a change in cell cycle distribution in V-79 cells, resulting in a dose-dependent reduced fraction of S-phase and an increased fraction of G1- and G2 + M-phase cells. However, these kinetic changes cannot explain the observed radioprotection of asynchronous populations, since purified G1 cells are more radiosensitive. Furthermore, cells synchronized in G1 by centrifugal elutriation were shown to be protected by dexamethasone to the same extent as was the unsorted population, thereby ruling out the mechanism of protection being a redistribution in the cell cycle.
由于有报道称地塞米松是中国仓鼠V - 79细胞的辐射防护剂,具有潜在的临床意义,因此测试了地塞米松处理对其他五种培养的哺乳动物细胞系(包括两个人类细胞系)放射敏感性的影响,并对V - 79细胞的保护机制进行了初步研究。与其他已发表的结果一致,我们发现用地塞米松处理V - 79细胞会使D0增加1.3倍。相反,地塞米松对中国仓鼠卵巢细胞、小鼠纤维肉瘤、大鼠胶质瘤细胞、人二倍体成纤维细胞或人乳腺癌细胞的放射敏感性没有影响。为了研究地塞米松对V - 79细胞放射保护作用的机制,对细胞周期进行了检测。地塞米松处理会导致V - 79细胞的细胞周期分布发生变化,导致S期细胞比例呈剂量依赖性降低,G1期和G2 + M期细胞比例增加。然而,这些动力学变化无法解释观察到的异步群体的放射保护现象,因为纯化的G1期细胞对辐射更敏感。此外,通过离心淘析同步于G1期的细胞被证明受到地塞米松的保护程度与未分选群体相同,从而排除了保护机制是细胞周期重新分布的可能性。