Bernhard E J, Maity A, Muschel R J, McKenna W G
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Radiat Res. 1994 Dec;140(3):393-400.
The irradiation of cells results in delayed progression through the G2 phase of the cell cycle. Treatment of irradiated HeLa cells with caffeine greatly reduces the G2-phase delay, while caffeine does not alter progression of cells through the cell cycle in unirradiated cells. In this report we demonstrate that treatment of HeLa cells with the kinase inhibitor staurosporine, but not with the inhibitor H7, also results in a reduction of the G2-phase arrest after irradiation. Cell cycle progression in unirradiated cells is unaffected by 4.4 nM (2 ng/ml) staurosporine, which releases the radiation-induced G2-phase arrest. In HeLa cells, the G2-phase delay after irradiation in S phase is accompanied by decreased expression of cyclin B1 mRNA. Coincident with the reduction in G2-phase delay, we observed an increase in cyclin B1 mRNA accumulation in irradiated, staurosporine-treated cells compared to cells treated with irradiation alone. Caffeine treatment of irradiated HeLa cells also resulted in an elevation in the levels of cyclin B1 message. These results support the hypothesis that diminished cyclin B1 mRNA levels influence G2-phase arrest to some degree. The findings that both staurosporine and caffeine treatments reverse the depression in cyclin B1 expression suggest that these two compounds may act on a common pathway of cell cycle control in response to radiation injury.
细胞受到辐射会导致其在细胞周期的G2期进程延迟。用咖啡因处理受辐射的HeLa细胞可大大减少G2期延迟，而咖啡因不会改变未受辐射细胞在细胞周期中的进程。在本报告中，我们证明用激酶抑制剂星形孢菌素处理HeLa细胞，而不是用抑制剂H7处理，也会导致辐射后G2期停滞的减少。4.4 nM（2 ng/ml）的星形孢菌素不会影响未受辐射细胞的细胞周期进程，但它能解除辐射诱导的G2期停滞。在HeLa细胞中，S期受辐射后的G2期延迟伴随着细胞周期蛋白B1 mRNA表达的降低。与G2期延迟的减少相一致，我们观察到与仅接受辐射处理的细胞相比，经辐射且用星形孢菌素处理的细胞中细胞周期蛋白B1 mRNA的积累增加。用咖啡因处理受辐射的HeLa细胞也会导致细胞周期蛋白B1信息水平的升高。这些结果支持这样一种假说，即细胞周期蛋白B1 mRNA水平的降低在一定程度上影响G2期停滞。星形孢菌素和咖啡因处理都能逆转细胞周期蛋白B1表达的降低，这一发现表明这两种化合物可能作用于细胞周期控制的共同途径以应对辐射损伤。
