Muschel R J, Zhang H B, McKenna W G
Department of Pathology, University of Pennsylvania, Philadelphia 19104.
Cancer Res. 1993 Mar 1;53(5):1128-35.
Ionizing radiation induces a G2 delay in eukaryotic cells. Since mitotic cyclins are required to trigger the transition from G2 into and through mitosis, we chose to investigate their expression after irradiation in HeLa cells. In normally cycling HeLa cells, both cyclin A and B mRNA and protein levels rise dramatically in G2/M and rapidly fall coincident with the completion of mitosis. The rise of cyclin A mRNA at the S/G2 boundary slightly precedes that of cyclin B mRNA. Although the peaks of expression of each of these molecules overlap, cyclin A mRNA and protein diminish before cyclin B. After irradiation in S, cyclin A mRNA and protein levels rose with the same kinetics as in the controls, but ultimately exceeded the levels seen in the control population. Cyclin A mRNA and protein levels remained high throughout the G2 delay induced by irradiation. In contrast, cyclin B mRNA and protein levels did not rise as the irradiated cells entered G2/M. Only later, before the irradiated cells exited from G2/M, did levels of cyclin B reach the levels seen in the unirradiated controls. The decreased amount of cyclin B mRNA and protein was inversely proportional to the dose of radiation. These data indicate that irradiation that results in a G2 delay appears to block cells at a point after production of cyclin A but before cyclin B can be fully expressed and that cells do not exit from the delay until cyclin B is again expressed. Thus, cyclin A and cyclin B expression respond differentially to radiation, with cyclin A rising at the same time as the control and to even higher levels than that seen in the controls, whereas cyclin B shows a temporal delay in expression.
电离辐射可诱导真核细胞出现G2期延迟。由于有丝分裂周期蛋白是触发从G2期进入有丝分裂及完成有丝分裂所必需的，我们选择研究HeLa细胞受辐射后它们的表达情况。在正常循环的HeLa细胞中，周期蛋白A和B的mRNA及蛋白水平在G2/M期显著升高，并在有丝分裂完成时迅速下降。周期蛋白A mRNA在S/G2边界处的升高略早于周期蛋白B mRNA。尽管这些分子各自的表达峰值重叠，但周期蛋白A的mRNA和蛋白在周期蛋白B之前减少。在S期受辐射后，周期蛋白A的mRNA和蛋白水平以与对照相同的动力学上升，但最终超过了对照群体中的水平。在辐射诱导的整个G2期延迟过程中，周期蛋白A的mRNA和蛋白水平一直保持较高。相比之下，当受辐射细胞进入G2/M期时，周期蛋白B的mRNA和蛋白水平并未升高。只是在受辐射细胞从G2/M期退出之前，周期蛋白B的水平才达到未受辐射对照中的水平。周期蛋白B的mRNA和蛋白量的减少与辐射剂量成反比。这些数据表明，导致G2期延迟的辐射似乎在周期蛋白A产生后但周期蛋白B能够完全表达之前的某个点阻断细胞，并且细胞在周期蛋白B再次表达之前不会从延迟中退出。因此，周期蛋白A和周期蛋白B的表达对辐射的反应不同，周期蛋白A与对照同时升高且水平甚至高于对照，而周期蛋白B在表达上表现出时间延迟。
