Crompton N E, Hain J, Jaussi R, Burkart W
Institute for Medical Radiobiology, University of Zürich, Switzerland.
Radiat Res. 1993 Sep;135(3):372-9.
We show here that the arrests of cells in G2 phase of the cell cycle induced by either staurosporine or ionizing radiation are closely related phenomena governed by a common kinase signaling pathway. The protein kinase inhibitor staurosporine induces a complete G2-phase arrest in exponentially growing TK6 human lymphoblastoid and V79 Chinese hamster fibroblast cells. Both cell types are equally sensitive to the kinase inhibitor and the arrest is dependent on its continued presence. Caffeine completely abrogates this arrest at concentrations comparable to those which abrogate radiation-induced G2-phase arrest. The kinetics of caffeine-induced release of both kinds of arrest are essentially identical. The activity of p34cdc2 kinase was also found to increase in a parallel fashion after caffeine-induced release of both kinds of arrest. As opposed to those transformed cell types which arrest only in G2 phase in response to staurosporine, immortalized C3H 10T1/2 fibroblasts and Muntjak skin fibroblasts display both G1- and G2-phase arrests. The results suggest that staurosporine and radiation interact with regulatory pathways in the cell cycle, and specifically with a caffeine-sensitive signal transduction pathway which recognizes DNA damage, regulates the G2/M-phase transition, and attenuates the biological consequences of radiation exposure.
我们在此表明，由星形孢菌素或电离辐射诱导的细胞周期G2期阻滞是密切相关的现象，受共同的激酶信号通路调控。蛋白激酶抑制剂星形孢菌素可使指数生长的TK6人淋巴母细胞和V79中国仓鼠成纤维细胞完全阻滞于G2期。这两种细胞类型对该激酶抑制剂同样敏感，且阻滞依赖于其持续存在。咖啡因在与消除辐射诱导的G2期阻滞浓度相当的情况下，能完全消除这种阻滞。咖啡因诱导的两种阻滞释放的动力学基本相同。在咖啡因诱导两种阻滞释放后，还发现p34cdc2激酶的活性以平行方式增加。与那些仅在G2期对星形孢菌素产生阻滞反应的转化细胞类型不同，永生化的C3H 10T1/2成纤维细胞和印度麂皮肤成纤维细胞表现出G1期和G2期阻滞。结果表明，星形孢菌素和辐射与细胞周期中的调控途径相互作用，特别是与一种对咖啡因敏感的信号转导途径相互作用，该途径识别DNA损伤、调节G2/M期转换，并减轻辐射暴露的生物学后果。
