抄録
Following whole-body exposure of p53(-/-) and p53(+/+) mice to fast neutrons from a 1-W reactor UTR-KINKI, the frequency of micronuclei (MNs) was measured in reticulocytes at multiple time points after exposure. The resulting time-course curve of MN frequency showed a clear peak 36 h after exposure, irrespective of the dose used. We calculated the area beneath the curve (A) as an index of total MN response. The A values for p53(-/-) and p53(+/+) mice did not differ significantly, suggesting near normal sensitivity of p53(-/-) mice to fast neutrons for MN induction. Since p53(-/-) mice are hypersensitive to X-ray-induction of MNs in reticulocytes, this finding implies that p53-gene function is not involved as a defense of somatic tissues from DNA damage caused by high-LET radiation. This hypothesis was tested by examining the frequency of apoptotic lymphocytes in the thymus and spleen of p53(-/-) mice 4 h after exposure to fast neutrons. In both organs, the frequency of apoptotic cells increased significantly over the control level. For example, the frequency in mice exposed to a neutron dose of 0.2 Gy relative to the control was 7.2±2.4 in thymus and 7.2±1.9 in spleen. These results support the conclusion that apoptosis induced by high-LET radiation is controlled by gene(s) other than p53.
