Maity A, Hwang A, Janss A, Phillips P, McKenna W G, Muschel R J
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, USA.
Oncogene. 1996 Oct 17;13(8):1647-57.
Exposure of cells to DNA damaging agents results in a G2 arrest. Exposure of HeLa cells to camptothecin, etoposide or nitrogen mustard for 1 h in S phase resulted in delayed expression of cyclin B1 mRNA during the G2 arrest. Initially the levels of cyclin B1 protein were low as well; however, with extended time the cells blocked in G2 regained higher levels of cyclin B1 protein. In the case of cells treated with nitrogen mustard the higher levels coincided with cells exiting the G2 block into G1. However, with camptothecin or etoposide treatment, while the accumulation of cyclin B1 protein was delayed, its levels eventually surpassed peak levels seen in control cells, in spite of the fact that cells were still blocked in G2. These cells did not continue to progress through the cell cycle indicating further complexity to the mechanisms underlying the G2 block. Decreased transcription and stability of cyclin B1 mRNA were shown to occur after treatment with these DNA damaging agents. These results indicate that suppression of cyclin B1 mRNA expression is one consequence of DNA damage in HeLa cells.
将细胞暴露于DNA损伤剂会导致G2期阻滞。在S期将HeLa细胞暴露于喜树碱、依托泊苷或氮芥1小时，会导致在G2期阻滞期间细胞周期蛋白B1 mRNA的表达延迟。最初，细胞周期蛋白B1蛋白的水平也很低；然而，随着时间的延长，阻滞在G2期的细胞恢复了较高水平的细胞周期蛋白B1蛋白。在用氮芥处理的细胞中，较高水平与细胞从G2阻滞进入G1期同时出现。然而，在用喜树碱或依托泊苷处理时，虽然细胞周期蛋白B1蛋白的积累延迟，但其水平最终超过了对照细胞中的峰值水平，尽管细胞仍阻滞在G2期。这些细胞并未继续通过细胞周期，这表明G2阻滞背后的机制更加复杂。在用这些DNA损伤剂处理后，细胞周期蛋白B1 mRNA的转录和稳定性降低。这些结果表明，抑制细胞周期蛋白B1 mRNA表达是HeLa细胞DNA损伤的一个后果。
