Low-dose-rate radiation attenuates the response of the tumor suppressor TP53.
Low-dose-rate radiation attenuates the response of the tumor suppressor TP53.
复制标题
低剂量率辐射会减弱肿瘤抑制因子 TP53 的反应。
作者：
T. Ohnishi;Xinjiang Wang;A. Takahashi;K. Ohnishi;Yosuke Ejima
急性低剂量照射（0.1-1 Gy, 1.33 Gy/min）人胶质母细胞瘤细胞系a -172细胞，诱导TP53（以前称为p53）和CDKN1A（以前称为WAF1）的剂量依赖性的单阶段积累。相比之下，慢性γ辐射（0.001 Gy/min）产生明显的双相TP53积累反应，第一个峰在1.5 h (0.09 Gy)，第二个峰在10 h （0.54 Gy）。值得注意的是，当细胞预先接受24小时（1.44 Gy）或50小时（3 Gy）的慢性γ射线照射时，它们不再对急性挑战性剂量做出反应，从而产生TP53通路的剂量依赖性反应。这些发现表明，低剂量率的慢性照射改变了tp53依赖的信号转导途径。由于长期暴露于辐射，TP53通路的磨损可能对辐射防护具有重要意义。
Acute low-dose irradiation (0.1-1 Gy, 1.33 Gy/min) of cells of a human glioblastoma cell line, A-172, induced a dose-dependent monophasic accumulation of TP53 (formerly known as p53) and CDKN1A (formerly known as WAF1). In contrast, chronic gamma irradiation (0.001 Gy/min) produced a clear biphasic response of accumulation TP53 with the first peak at 1.5 h (0.09 Gy) and the second peak at 10 h (0.54 Gy). Significantly, when the cells were preirradiated with a chronic dose of gamma irradiation for 24 h (1.44 Gy) or 50 h (3 Gy), they no longer responded to an acute challenging dose to produce a dose-dependent response of the TP53 pathway. These findings suggest that chronic irradiation at low dose rate alters the TP53-dependent signal transduction pathway. Wearing away of the TP53 pathway by chronic exposure to radiation may have important implications for radiation protection.