Yoshida, K., Hirabayashi, Y., Wada, S., Watanabe, F., Watanabe, K., Aizawa, S. and Inoue, T. 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. Radiat. Res. 167, 703–710 (2007).
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.