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.
Ohnishi
T
T
Department of Biology, Nara Medical University, Kashihara, Nara, Japan.
Takahashi
A
A
Ohnishi
K
K
Yonezawa
M
M
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2; D011836:Radiation Tolerance; D015398:Signal Transduction / Q000528:radiation effects*; D013154:Spleen / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism* / Q000528:radiation effects; D014965:X-Rays; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein