Zellars R C, Naida J D, Davis M A, Lawrence T S
Department of Radiation Oncology, University of Michigan, Ann Arbor 48109-0582, USA.
Radiat Oncol Investig. 1997;5(2):43-9. doi: 10.1002/(SICI)1520-6823(1997)5:2<43::AID-ROI1>3.0.CO;2-J.
Substantial controversy surrounds our understanding of the effect of p53 status on radiation sensitivity. To assess directly the role of p53 expression on radiation sensitivity, we chose a conditional expression system using a temperature-sensitive murine p53 that permitted each cell line to act as its own control. We found that the conditional expression of wild type p53 induced cell death (both apoptotic and nonapoptotic), changes in cell cycle distribution (arrest in G1 and G2, which resulted in a marked depletion of S-phase cells and an increase in the fraction of cells in G2), and an increase in the radiation resistance of G1 cells. These counterbalancing effects resulted in no significant effect on overall radiosensitivity. These findings demonstrate that wild type p53 function can produce a variety of effects that can modulate radiation sensitivity and may explain why p53 status alone has not been a strong predictor of radiosensitivity.
围绕我们对p53状态对辐射敏感性影响的理解存在大量争议。为了直接评估p53表达对辐射敏感性的作用，我们选择了一种条件表达系统，使用温度敏感型小鼠p53，使每个细胞系都能作为自身对照。我们发现野生型p53的条件表达诱导细胞死亡（包括凋亡和非凋亡）、细胞周期分布改变（G1期和G2期阻滞，导致S期细胞显著减少，G2期细胞比例增加）以及G1期细胞辐射抗性增加。这些相互抵消的效应导致对总体辐射敏感性无显著影响。这些发现表明野生型p53功能可产生多种能调节辐射敏感性的效应，这可能解释了为何仅p53状态并非辐射敏感性的有力预测指标。
