Frequent p53 mutation in mouse tumors induced by repeated beta-irradiation.

On examination of cDNA of the p53 gene in 65 murine tumors of the skin and bone produced by repeated exposure to a suprathreshold dose of 1-8 Gy of 90Sr-90Y beta-radiation per exposure, we found 20 cases of mutation: 11 minute deletions (loss of 1-24 bp), including two cases possibly due to aberrant splicing; three insertions of 4-8 bp; and six base-pair substitutions, including four at CpG sites, three being identical changes at codon 122 (a p53 hot spot). All but one of these mutations were confined to the central region of the p53 gene. From frameshifts created by deletions and insertions, the minimum size of the mutant p53 proteins found in these tumors was estimated to be 55% of the intact size. Cells of 17 of 19 tested tumors with p53 mutation were positive for immunostaining of p53 proteins accumulated in the nuclei and so were clearly different from nonneoplastic cells. Ha-ras mutation was absent in these tumors, indicating that repeated beta-irradiation created a cell-growth stimulating effect similar to that of ras mutation.