Abstract
The p53 gene plays a key role in the cellular response to genotoxic stress. It is thought that p53 deficiency results in increased survival of cells with DNA damage, either by failure of DNA repair, or by failed deletion of mutation-bearing cells. The in vivo T-cell receptor (TCR) assay detects somatic mutation with a high sensitivity. Mutant CD4+ lymphocytes, are found to be CD3-CD4+ by flow cytometry. The number of these mutant cells increases in humans and mice following exposure to radiation. At 8 weeks of age, wild p53(+/+) mice, heterozygous p53(+/-) mice and null p53(-/-) mice were given a whole-body acute dose of 3Gy X-rays. TCR assays were done at various time intervals between 9 days and 40 weeks after exposure. In p53(+/+) mice, the TCR-MF reached a peak level 9 days after irradiation, and TCR-MF decreased and reached background levels within 8 weeks. In p53(+/-) mice, the TCR-MF reached a peak level 9 days after irradiation, and TCR-MF decreased and reached background levels within 28 weeks. However, TCR-MF increased again 36 weeks after irradiation. In p53(-/-) mice, the TCR-MF reached a peak level 9 days after irradiation, and high frequency followed. These findings show that loss of p53 function becomes relevant to the acquisition of delayed mutations.
