Low-dose-rate radiation attenuates the response of the tumor suppressor TP53

Acute low-dose irradiation (0.1-1 Gy, 1.33 Gy/min) of cells of a human glio blastoma cell line, A-172, induced a dose-dependent monophasic accumulation of TP53 (formerly known as p53) and CDKN1A (formerly known as as WAF1). In contrast, chronic gamma irradiation (0.001 Gy/min) produced a clear biphas ic 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 prei rradiated 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 Endings suggest that chronic irradiation at low dose rate alters the TP53-dependent signal trans duction pathway, Wearing away of the TP53 pathway by chronic exposure to ra diation may have important implications for radiation protection. (C) 1999 by Radiation Research Society.