Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice

Nat Genet. 1993 Nov;5(3):225-9. doi: 10.1038/ng1193-225.

Abstract

Using gene targeting techniques, mice that have been generated with two germ-line p53 null alleles (homozygotes) develop normally but are highly susceptible to early onset spontaneous tumours. Here, we show that mice with a single null p53 allele (heterozygotes) produced in the same way are also susceptible to spontaneous tumours, but with a delayed onset compared to homozygotes. The most frequent tumour type in homozygotes was malignant lymphoma; in heterozygotes, osteosarcomas and soft tissue sarcomas predominated. Heterozygous mice treated with a liver carcinogen, dimethylnitrosamine, showed a decreased survival time in comparison to treated wild type mice, suggesting that the p53-deficient mice may be useful for some in vivo carcinogenesis assays.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Dimethylnitrosamine
  • Genes, p53*
  • Heterozygote
  • Homozygote
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / chemically induced
  • Neoplasms, Experimental / genetics*

Substances

  • Dimethylnitrosamine