Abstract
Normal function of the p53 gene is integral to the cellular response to genotoxic stress. In order to investigate the in vivo role of p53 in surveillance against mutation, and particularly to address the significance of p53-dependent apoptosis, we have used wild-type p53(+/+) and null p53(-/-) mice to determine the mutant frequency at the TCR locus following exposure to gamma-rays. The induced mutant frequencies at 3Gy were 15.6 x 10−4 and 33.2 x 10−4 for p53(+/+) and p53(-/-) mice, respectively. However, when the dose rate was reduced from 61 to 0.07 Gy/h, the mutant frequency at the TCR locus did not increase at all for p53(+/+) mice, whereas the dose of 3Gy remained mutagenic for p53(-/-) mice, which are unable to carry out p53-dependent apoptosis. These results indicate that p53 deficiency should lead to an increased mutant frequency by failed elimination of the mutagenic damage from the irradiated tissues. [J Radiat Res 44:376 (2003)]
