p53 (TRP53) deficiency-mediated antiapoptosis escape after 5 Gy X irradiation still induces stem cell leukemia in C3H/He mice: comparison between whole-body assay and bone marrow transplantation (BMT) assay.
Mice exposed to a lethal dose of radiation were repopulated with heterozygous p53(+/-) (TRP53(+/-)) bone marrow cells and then exposed to doses of 1, 3 and 5 Gy 1 month later. This resulted in the transplanted bone marrow-specific diseases other than competitively induced nonhematopoietic neoplasms. Interestingly, the present study showed a high frequency of stem cell leukemia, i.e., leukemias characterized by a lack of differentiation due also to p53 deficiency, even after 5 Gy irradiation. The frequencies of stem cell leukemias (and those of total hematopoietic malignancies) were 16% (24%) at 1 Gy and 45% (75%) at 3 Gy. Furthermore, markedly high incidences of stem cell leukemias were observed at 5 Gy in p53(+/-) mice, i.e., 87% (100%) in the transplantation assay and 60% (83.3%) in the whole-body assay, whereas a conventional whole-body assay induced only 14% in wild-type mice. The high incidence of stem cell leukemias observed in this study using heterozygous p53-deficient mice agrees with results of a previous study of homozygous p53-deficient mice and is consistent with the high frequency of loss of heterozygosity in the p53 wild-type allele observed in leukemias. This suggests that the target cells for radiation-induced stem cell leukemias may be p53-deficient hematopoietic stem cells.
Yoshida
Kazuko
K
Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba, Japan. yosida@nirs.go.jp
Hirabayashi
Yoko
Y
Wada
Sachiko
S
Watanabe
Fumiko
F
Watanabe
Keiko
K
Aizawa
Shiro
S
Inoue
Tohru
T
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D016026:Bone Marrow Transplantation / Q000379:methods*; D007953:Leukemia, Radiation-Induced / Q000503:physiopathology* / Q000601:surgery*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011829:Radiation Dosage; D013234:Stem Cells / Q000528:radiation effects*; D016019:Survival Analysis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics; D014916:Whole-Body Irradiation
D016159:Tumor Suppressor Protein p53