Radiation Research · 1999 · 42 citations · 15 references
MedicineCell BiologyOncologyMolecular OncologyRadiation ProtectionRadiobiologyBiological Effects Of RadiationCellular Radiation ResponseLow-dose Radiation EffectsRadiation PhysiologyRadiation TherapyRadiation ToxicityCancer Cell RadiosensitivityCellular RadiosensitivityChronic Low-dose ExposureDose ResponseGamma Irradiation EffectsIrradiation EffectsLow-dose-rate Radiation ResponseSignal Transduction After Irradiation
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.
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WAF1, a potential mediator of p53 tumor suppression
Wafik S. El‐Deiry, Takashi Tokino, Victor E. Velculescu et al. · Cell · 1993 · 8.4K citations