The p53-deficient hemopoietic stem cells: their resistance to radiation-apoptosis, but lasted transiently.
Hemopoietic stem cells lacking with p53 are known to be resistant to radiation apoptosis: p53-product induces, on one hand, the cells that have been injured by radiation to stop cell-cycle at G, phase, and on the other hand the cells that have not been repaired to go into apoptosis. Thus, in the p53-deficient mice, the hemopoietic stem cells after graded dose of radiation show a flatter survival curve for radiation, i.e., like a curve for radio-resistant phenotype. However, we found the radio-resistance in the stem cell was only transient, and an apoptosis in p53-deficient hemopoietic stem cells, we made concentrated analysis including the end-labeling technique to detect double strand breaks of DNA. Results clearly showed that, according to the end-labeling for spleen colonies, the p53-deficiency showed rather higher incidence of apoptosis (30-50%) as compared with the wild-control (17%). Irradiation with 200cGy for the recipient mice two months after transplantation, showed an induction of higher incidence of hemopoietic malignancies, when the heterozygous marrow was repopulated, however, none of increase was observed in the recipient mice repopulated with the homozygous bone marrow. Clear difference between the hetero- and the homozygous in inducing hemopoietic malignancies with the 200cGy-radiation may be reflected by the different degree of delayed appearance of apoptosis during the development of the spleen colonies.
Hirabayashi
Y
Y
Department of Pathology, Yokohama City University School of Medicine, Japan.
Matsuda
M
M
Matumura
T
T
Mitsui
H
H
Sasaki
H
H
Tukada
T
T
Aizawa
S
S
Yoshida
K
K
Inoue
T
T
D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000473:pathology; D002453:Cell Cycle / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D019337:Hematologic Neoplasms / Q000453:epidemiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D007953:Leukemia, Radiation-Induced / Q000473:pathology; D051379:Mice; D011836:Radiation Tolerance; D012016:Reference Values; D013154:Spleen / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency*
D016159:Tumor Suppressor Protein p53