Spontaneous and Ionizing Radiation-induced Chromosomal Abnormalities in p53-deficient Mice

Chromosomal abnormalities have been assessed in 153-deficient mice. The in vivo frequency of spontaneous stable aberrations in bone marrow cells was elevated by approximately 20-fold in p53 nulls and 13-fold in p53 heterozygotes compared to wild-type. No excessive induction of stable aberrations by y-irradiation was observed, but p53 deficiency resulted in excess radiation-induced hyperploidy (>10-fold wild-type frequency). No influence of pS3 genotype on sister chromatid exchange or G2 chromatid damage was observed in mitogen-stimulated spleen cell cultures; however, a p53 effect on postirradiation mitotic entry was seen. Abnormalities in chromosome segregation and mitotic delay following irradiation in p53-deficient mice suggest a G2-M checkpoint role for p53 and are broadly consistent with data on tumorigenesis in these animals.