Abstract
Purpose: Previously, we reported that irradiation in young age induced delayed mutation, and that decrease function of p53 gene related to delayed mutation. In this study, we investigated the p53 gene function and mutations at old age in p53+/- mice after irradiation at several points.
Methods and Materials: p53+/- mice were received a whole-body dose of 3 Gy at 28 and 40 weeks of age. We evaluated TCR MFs after irradiation to 60 weeks of age, and apoptosis, loss of p53 alleles, p53 gene methylation, and protein expression of p53, p53ser15 and p21 at 60 weeks of age.
Results: We previously reported that in p53+/- mice that were received a whole-body dose of 3 Gy at 8 weeks of age, T-cell receptor (TCR) mutation frequencies (MFs) reached at a peak level at 10 weeks of age, decreased at spontaneous level at 20 weeks of age and re-increased from 40 weeks of age. At 60 weeks of age, TCR MFs and p53 gene methylation were higher in mice after irradiation at 40 weeks of ages compared to mice after irradiation at 28 weeks of ages. On the other hand, at 60 weeks of age, apoptosis and protein expression of p53, p53ser15 and p21 were lower in mice after irradiation at 40 weeks of ages compared to mice after irradiation at 28 weeks of ages.
Conclusion: We concluded that, because p53 would damage with age gradually, the delayed effect of irradiation was heavier when the mice received irradiation at older age.
