Pre-irradiation at a low dose-rate blunted p53 response.
We investigated whether chronic irradiation at a low dose-rate interferes with the p53-centered signal transduction pathway induced by radiation in human cultured cells and C57BL/6N mice. In in vitro experiments, we found that a challenge with X-ray irradiation immediately after chronic irradiation resulted in lower levels of p53 than those observed after the challenge alone in glioblastoma cells (A-172). In addition, the levels of p53-centered apoptosis and its related proteins after the challenge were strongly correlated with the above-mentioned phenomena in squamous cell carcinoma cells (SAS/neo). In in vivo experiments, the accumulation of p53 and Bax, and the induction of apoptosis were observed dose-dependently in mouse spleen at 12 h after a challenge with X-rays (3.0 Gy). However, we found significant suppression of p53 and Bax accumulation and the induction of apoptosis 12 h after challenge irradiation at 3.0 Gy with a high dose-rate following chronic pre-irradiation (1.5 Gy, 0.001 Gy/min). These findings suggest that chronic pre-irradiation suppressed the p53 function through radiation-induced signaling and/or p53 stability.
Takahashi
Akihisa
A
Department of Biology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan. atakahas@naramed-u.ac.jp
D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000528:radiation effects; D016158:Genes, p53 / Q000528:radiation effects*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D015398:Signal Transduction / Q000528:radiation effects; D013154:Spleen / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53