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Cancer Prevention Studies in p53-Deficient MiceNational Cancer Institute, Bethesda, Maryland 20892
National Cancer Institute, Bethesda, Maryland 20892
Baylor College of Medicine, Houston, Texas 77030
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Future progress in mechanism-based cancer prevention research may be facilitated by animal models displaying specific genetic susceptibilities for cancer, such as mice defi cient in 1 (+/-) or both (-/-) alleles of the p53 tumor suppressor gene. We observed in p53-/- mice that calorie restriction (CR) increased the latency of spontaneous tumor development (mostly lymphomas) by approximately 75%, decreased serum insulin-like growth factor-1 (IGF-1) and leptin levels, slowed thymocyte cell cycle traverse, and induced apoptosis in immature thymocytes. In p53+/- mice, CR and a 1 d/wk fast each delayed spontaneous tumor development (a mix of lymphomas, sarcomas, and epithelial tumors) and decreased serum IGF-1 and leptin levels, even when begun late in life. In p53+/- Wnt-1 transgenic mice, a mammary tumor model, the same interventions increased mammary tumor latency and reduced mean serum IGF-1 and leptin levels to <50 % of those of control mice. We capitalized on the susceptibility of p53+/- mice to chronic, low-dose aromatic amine—induced bladder carcinogenesis to develop a useful model for evaluating bladder cancer prevention approaches. These examples clearly indicate that mice with specific (and humanlike) genetic susceptibilities for cancer are powerful models for testing interventions that may inhibit carcinogenesis in humans.
Key Words: Nutrition • chemoprevention • transgenics • calorie restriction • insulin-like growth factor-1 • leptin
Toxicologic Pathology, Vol. 29, No. 1,
137-141 (2001) |
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