Takahashi Akihisa
Department of Biology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
J Radiat Res. 2002 Mar;43(1):1-9. doi: 10.1269/jrr.43.1.
We investigated whether chronic irradiation at a low dose-rate interferes with the p53-centered signal transduction pathway induced by radiation in human cultured cells and C57BL/6N mice. In in vitro experiments, we found that a challenge with X-ray irradiation immediately after chronic irradiation resulted in lower levels of p53 than those observed after the challenge alone in glioblastoma cells (A-172). In addition, the levels of p53-centered apoptosis and its related proteins after the challenge were strongly correlated with the above-mentioned phenomena in squamous cell carcinoma cells (SAS/neo). In in vivo experiments, the accumulation of p53 and Bax, and the induction of apoptosis were observed dose-dependently in mouse spleen at 12 h after a challenge with X-rays (3.0 Gy). However, we found significant suppression of p53 and Bax accumulation and the induction of apoptosis 12 h after challenge irradiation at 3.0 Gy with a high dose-rate following chronic pre-irradiation (1.5 Gy, 0.001 Gy/min). These findings suggest that chronic pre-irradiation suppressed the p53 function through radiation-induced signaling and/or p53 stability.
我们研究了低剂量率慢性照射是否会干扰人培养细胞和C57BL/6N小鼠中辐射诱导的以p53为中心的信号转导通路。在体外实验中，我们发现，在慢性照射后立即进行X射线照射刺激，胶质母细胞瘤细胞（A-172）中p53的水平低于单独刺激后观察到的水平。此外，刺激后以p53为中心的凋亡及其相关蛋白水平与鳞状细胞癌细胞（SAS/neo）中的上述现象密切相关。在体内实验中，用X射线（3.0 Gy）刺激后12小时，在小鼠脾脏中观察到p53和Bax的积累以及凋亡的诱导呈剂量依赖性。然而，我们发现，在慢性预照射（1.5 Gy，0.001 Gy/分钟）后，以高剂量率进行3.0 Gy刺激照射后12小时，p53和Bax的积累以及凋亡的诱导受到显著抑制。这些发现表明，慢性预照射通过辐射诱导的信号传导和/或p53稳定性抑制了p53功能。
