Elevated in vivo frequencies of mutant T cells with altered functional expression of the T-cell receptor or hypoxanthine phosphoribosyltransferase genes in p53-deficient mice

We have studied the effects of a defect in the p53 gene on spontaneous and radiation-induced somatic mutation frequencies in vivo by measuring T-cell receptor (TCR) and hypoxanthine phosphoribosyltransferase (HPRT) mutant fre quencies (MFs) in p53 deficient mice both before and after exposure to X-ir radiation. In the absence of irradiation, the TCR and HPRT mutant frequenci es were roughly two-fold higher in p53 null (-/-) mice than in wild-type (/+) mice. Unexpectedly, the TCR and HPRT MFs were slightly lower in heteroz ygote p53 (+/-) than in wild-type (+/+) mice., however. After 2 weeks 2 Gy whole body irradiation the TCR and HPRT MFs were about two-fold higher in t he p53 null (-/-) and p53 (+/-) mice than in the wild-type. Taken together, these findings suggest that a defect in the p53 gene may lead to TCR and H PRT mutants being recovered at higher frequencies in both irradiated and un irradiated mice, but it should be emphasized that the effects we have obser ved are not particularly strong, albeit that they are statistically signifi cant. Interestingly, several of the highest TCR MF values that we observed in the course of our experiments were recorded in p53 (-/-) animals that ha d developed thymomas and hence appeared to be cancer prone. (C) 2001 Elsevi er Science B.V. All rights reserved.