Tumor suppressor p53 response is blunted by low-dose radiation

To estimate the effects of space radiation on health of space crews, we aimed to clarify whether g-ray-irradiation at a low-dose-rate interferes in a p53 centered signal transduction pathway induced by radiation in human cultured cells and CB-17 Icr+/+ mice. In vitro experiments, the human cultured squamous cell carcinoma cells (SAS/neo) were examined for cellular levels of p53 and Bax, and the incidence of apoptosis after irradiation at a low-dose-rate (1 mGy/min) or a high-dose-rate (1 Gy/min). It was found that challenging irradiation-induced apoptosis was depressed by chronic irradiation at 1.5 Gy for 25 h with the depression of p53 and Bax accumulation. In vivo experiments, a significant suppression of Bax and apoptosis induced by challenging irradiation at 3.0 Gy was observed when the mice were pre-irradiated chronically at 1.5 Gy for 25 h in the spleen of CB-17 Icr+/+ mice. These findings suggest that chronic pre-irradiation suppressed p53 function through radiation-induced signaling and/or p53 stability.