Abstract
Previously in this meeting, we reported that irradiation in young age induced delayed mutation, and that decrease function of p53 gene related to delayed mutation. In a word, in mice that were received a whole-body dose of 3 Gy at 8 weeks of age, T-cell receptor (TCR) mutation frequencies (MFs) increased from 60 weeks of age in p53(+/+) mice and from 40 weeks of age in p53(+/-) mice much higher than in the control mice. Also, we showed the decrease of apoptosis activity induced by radiation, the rise in translocation frequency in 11th chromosome and p53 genome mutation in CD3-CD4+ cell from spleen. In this study, we investigated that the protein expression of p53 and the related gene by western blot method and the p53 loss of heterozygosity (LOH) by PCR. p53(+/+) mice and p53(+/-) mice were received a whole-body dose of 3 Gy at 8 weeks of age. Mice were sacrificed at 10, 24, 56 (p53(+/-) mice only) and 72 (p53(+/+) mice only) weeks of age. The levels of p53 and p21 protein increased gradually with ageing. These protein levels in the irradiated group were smaller than that in the control group. The levels of p53ser15/18, ATM and ATR protein decreased in old mice and furthermore these protein levels in the irradiated group were smaller than that in the control group. Some old mice showed LOH of p53. We suggested that the decreased activity of ATM-p53 and ATR-p53 pathway and LOH of p53 were related to the delayed mutation after irradiation in young age.
