Abrogation of the G2 checkpoint results in differential radiosensitization of G1 checkpoint-deficient and G1 checkpoint-competent cells.
Abrogation of the G2 checkpoint results in differential radiosensitization of G1 checkpoint-deficient and G1 checkpoint-competent cells.
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发表时间：
1995-04
期刊：
影响因子：
11.2
通讯作者：
K. Russell;Wiens Lw;G. Demers;D. Galloway;Plon Se;M. Groudine
中科院分区：
文献类型：
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作者：
K. Russell;Wiens Lw;G. Demers;D. Galloway;Plon Se;M. Groudine
我们已经检查了废除G2检查点对G1检查点熟练和G1检查点缺陷细胞的放射敏感性的影响。用人乳头瘤病毒16型E6癌基因转导A549人肺腺癌细胞，以消除其辐射诱导的G1期阻滞。与仅用载体转导的对照A549细胞相比，这些E6+细胞表现出辐射抗性的剂量依赖性增加。用2 mM咖啡因处理（96 h）导致E6+和对照细胞中细胞G2检查点的消除，以及对两种细胞系的差异放射增敏作用，使得E6+克隆和载体对照变得同样放射敏感。这些数据表明，由于p53介导的G1检查点的缺失而具有放射抗性的人肿瘤可以通过废除G2检查点而变得放射敏感。这些结果对癌症治疗的影响进行了讨论。
We have examined the effect of abrogation of the G2 checkpoint on the radiosensitivity of G1 checkpoint-proficient and G1 checkpoint-deficient cells. A549 human lung adenocarcinoma cells were transduced with the E6 oncogene of the human papillomavirus type 16 to eliminate their radiation-induced G1 arrest. These E6+ cells exhibited a dose-dependent increase in radiation resistance compared to control A549 cells transduced with the vector alone. Treatment (96 h) with 2 mM caffeine resulted in an abrogation of the cellular G2 checkpoint in both E6+ and control cells and a differential radiosensitizing effect on the two cell lines such that the E6+ clones and the vector controls became equally radiosensitive. These data show that human tumors which are radioresistant due to the loss of the p53-mediated G1 checkpoint can be made radiosensitive by abrogation of the G2 checkpoint. The implications of these results for cancer therapy are discussed.