Radiation response of apoptosis in C57BL/6N mouse spleen after whole-body irradiation.
OBJECTIVE
Primary conditioning low dose irradiation suppresses the molecular responses against secondary challenge high dose irradiation; this phenomenon has been termed the radioadaptive response. The mechanism of the radioadaptive response is not yet clear. This study was undertaken to elucidate the radiation response of apoptosis in mouse spleen after whole-body irradiation.


METHODS
The induction of apoptosis was analysed in the spleens of C57BL/6N mice after chronic irradiation with gamma-rays at 1.5 Gy (0.001 Gy/min for 25 h) followed by challenge irradiation with X-rays at 3.0Gy (1 Gy/min).


RESULTS
Accumulation of p53 and Bax, and the induction of apoptosis were observed dose-dependently in mouse spleen 12 h after acute irradiation at a high dose-rate. However, it was found that there was significant suppression of the accumulation of p53 and Bax, and induction of apoptosis 12 h after challenge irradiation at 3.0Gy at a high dose-rate following chronic preirradiation at 1.5Gy at a low dose-rate. In addition, the combination of pre-irradiation at 1.5Gy at a high dose-rate and challenge irradiation at 3.0Gy at a high dose-rate could not suppress the accumulation of p53 and Bax or the induction of apoptosis.


CONCLUSIONS
Chronic pre-irradiation at a low dose-rate suppressed Bax-mediated apoptosis. These findings suggest that the radioadaptive response in mouse spleen may be due to a suppression of p53-mediated apoptosis.
Takahashi
A
A
Department of Biology, Nara Medical University, Kashihara, Nara 634-8521, Japan.
Ohnishi
K
K
Asakawa
I
I
Kondo
N
N
Nakagawa
H
H
Yonezawa
M
M
Tachibana
A
A
Matsumoto
H
H
Ohnishi
T
T
D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013154:Spleen / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014916:Whole-Body Irradiation; D051028:bcl-2-Associated X Protein
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