Abstract
(Purpose) Previously, we reported that irradiation in young age induced delayed mutation, which were related to dysfunction of p53. In this study, we evaluated the effect of irradiation in young age on lifespan. We analyzed the time-course of the cell numbers and cell cycles of myelocyte and lymphocyte in bone marrow, and also the time-course of cell proliferation of splenocyte. Furthermore, we evaluated the protein expressions of p53 and the related gene. (Materials and Methods) We used p53(+/-) mice and p53(+/+) mice, which were irradiated a whole-body dose of 3 Gy at 8 weeks of age (irradiated group). p53(+/-) mice were sacrificed at 24 and 56 weeks (old mice) of age and p53(+/+) mice at 40 and 72 weeks (old mice) of age. Cell numbers and cell cycles of bone marrow cells from femurs and tibias were analyzed. In p53(+/+) mice, cell proliferation of splenocyte, which was stimulated by Concanavalin A, was measured. From 0 to 24 h after old p53(+/+) mice were irradiated a whole-body dose of 3 Gy, the protein expressions in spleen of p53, p21 and MDM2 in cytoplasm and nucleus were analyzed by Western blot methods. The rate of p53 allele was analyzed by PCR in CD3-CD4+ cells in spleen. (Results) Lifespan was shortened by irradiation at 8 weeks of age. In old mice, the cell number of lymphocyte in bone marrow in irradiated group decreased compared to that in non-irradiated group. In old p53(+/-) mice, cell cycle of lymphocyte was accelerated. The proliferation in splenocyte in p53(+/+) mice decreased with age, and the proliferation in irradiated group was much lower than that in non-irradiated group. In old p53(+/+) mice, the protein expressions of p53, p21 and MDM2 in irradiated group delayed compared to that in non-irradiated group. In old mice, the rate of p53 allele decreased in irradiated group compared to that in non-irradiated group. (Conclusion) We suggested that irradiation accelerated aging, and that, because of these failures of immune system and dysfunction of p53, the lifespan was shortened in irradiated mice.
