Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice.
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.
Harvey
M
M
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030.
McArthur
M J
MJ
Montgomery
C A
CA
Butel
J S
JS
Bradley
A
A
Donehower
L A
LA
D000818:Animals; D004128:Dimethylnitrosamine; D016158:Genes, p53; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*
D004128:Dimethylnitrosamine