Abstract
We have already reported that γ-irradiation with 3 Gy at 1.2 mGy/min was not mutagenic in TCR gene for p53(+/+) mice but mutagenic for p53(-/-) mice, and p53(-/-) mice kept the high frequencies of TCR mutation over the 2 months after irradiation. In order to elucidate the in vivo role of p53 gene in surveillance against mutation, we improved the method to observe the mutant frequency on TCR gene using a 3-color FACS analysis, which includes FITC-anti-CD3, PE-anti-CD4, and CyChrome-anti-CD44 monoclonal antibodies. We could detect the TCR mutant cells, which showed CD3- and CD4+, both in CD44- naive and CD44+ memory T cells after irradiation. The mutant frequencies of naive cells and memory cells at 6 weeks after irradiation were 11.4 and 17.9 (x 10-4) in p53(+/+) mice, and 32.7 and 64.3 (x 10-4) in p53(-/-) mice, respectively. These results indicate the high mutant frequency on TCR gene in p53(-/-) mice, especially in memory T cells. Previously we observed that the frequency of the cells dying by apoptosis after irradiation with 2 Gy greatly increased in p53(+/+) mice, but did not increase in p53(-/-) mice. Taken together, concerted DNA repair and p53-dependent apoptosis are likely to completely eliminate mutagenic damage at low doses or low dose-rates.
