RRC ID 11853
Author Sugihara T, Murano H, Nakamura M, Ichinohe K, Tanaka K.
Title p53-Mediated gene activation in mice at high doses of chronic low-dose-rate γ radiation.
Journal Radiat. Res.
Abstract The time course of the changes in the expression of p53-mediated genes in vivo after high doses of chronic low-dose-rate γ radiation remains unclear. Here we analyzed peripheral blood cell counts and the expression of p53-mediated genes in the spleens of mice chronically irradiated at low dose rate (0.0167 Gy/h) for 1-40 days. Low-dose-rate irradiation induced p53-dependent chronic decreases in white blood cell (WBC) counts in p53 wild-type mice. Upregulation of p53-mediated genes by low-dose-rate radiation was confirmed in the whole spleen cells from the p53 wild-type mice, while suppressed gene expression was observed in the spleen cells of p53-deficient mice. The expression of p21 and Bax in radiosensitive cells such as T and B lymphocytes from low-dose-rate irradiated mice at 10, 20, and 40 days were increased, although that of Mdm2 in both the lymphocytes was decreased at 20 and 40 days. Moreover, spleen weights for low-dose-rate irradiated mice were decreased at 20 and 40 days. Thus downregulation of Mdm2 in both T and B lymphocytes by low-dose-rate radiation may cause higher p53 activation; further, higher p53 expression may determine the radiosensitivity and cause a reduction in the spleen weights in low-dose-rate irradiated mice. These results indicate that p53 may be chronically activated by low-dose-rate radiation.
Volume 175(3)
Pages 328-35
Published 2011-3
DOI 10.1667/RR2446.1
PII 10.1667/RR2446.1
PMID 21388276
MeSH Animals B-Lymphocytes / metabolism B-Lymphocytes / radiation effects Blood Cell Count Dose-Response Relationship, Radiation Female Gamma Rays* Mice Radiation Dosage* Spleen / cytology T-Lymphocytes / metabolism T-Lymphocytes / radiation effects Time Factors Transcriptional Activation / radiation effects* Tumor Suppressor Protein p53 / deficiency Tumor Suppressor Protein p53 / metabolism*
IF 2.779
Times Cited 7
Mice C3H/HeN-TgH(p53)