Spontaneous and radiation-induced tumorigenesis in p53-deficient mice

To investigate the spontaneous and radiation induced tumorigenesis, tumor development and
molecular changes were examined in p53 gene-deficient mice. All of the null (p53 -/-) animals
died of leukemia, sarcoma, etc. before 12 months of age, and predominantly of lymphocytic
leukemia at the early age of 3 – 5 months, while heterozygous (p53+/-) and wild type (p53+/+)
animals survived more than 30 and 40 months, respectively. Half of the heterozygotes developed
sarcomas (osteosarcomas, rhabdomyosarcomas, hemangiomas), and some developed tumors in the
lung and liver; however, a lower incidence of leukemia was found. The onset of the tumor was late in
their lives in the heterozygotes, though the tumors grew rapidly. In the wild type mice, leukemia and
sarcomas were rarely observed. The 137Cs g-irradiation shortened the lifespan of the heterozygotes
with an earlier tumor development, though this effect was not evident in the null mice. Among the 54
spontaneous tumors studied in the heterozygotes, 12 (22.2%) showed loss of the wild type p53 allele
(loss of heterozygosity, LOH) and one functional mutation was found at exon 6 of the p53 gene. All
the LOH was found in leukemia and sarcomas, except in one breast carcinoma. D 2002 Elsevier
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