Different inducibility of radiation- or heat-induced p53 -dependent apoptosis after acute or chronic irradiation in human cultured squamous cell carcinoma cells

Abstract

Purpose : This study was undertaken to clarify the effects of acute or chronic pre-irradiation on the induction of p53 -dependent apoptosis by X-rays or heat shock. Materials and methods : Having an identical genotype except for p53 -status, the human cultured squamous cell carcinoma cells (SAS) were transfected with a mutant p53 gene (SAS/m p53) or neo alone (SAS/ neo) as a control. After acute X-irradiation (1Gy min -1) , chronic gamma-irradiation (0.001 Gy min -1) or heat shock (44°C), the cells were for the incidence of apoptotic bodies and DNA ladders, cellular levels of p53 and bax, and caspase-3 activity. Results : It was found that (1) a challenge treatment with X-rays (5.0 Gy) or heat shock (30 min) immediately after chronic pre-irradiation (1.5Gy) but not acute pre-irradiation (1.5 Gy) resulted in lower levels of apoptosis than those observed after challenge treatment only in SAS/ neo cells; (2) a challenge treatment-induced apoptosis was observed 48h after cessation of chronic pre-irradiation in SAS/ neo cells; (3) apoptosis was barely increased in SAS/m p53 cells; and (4) the levels of apoptosis-related proteins after challenge treatments were strongly correlated with the above phenomena. Conclusions : Chronic pre-irradiation at a low dose-rate suppressed induction of p53 -dependent apoptosis via bax and caspase-3. These findings suggest that chronic pre-irradiation suppressed p53 function through radiation-induced signalling and/or p53 stability.