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Cancer Prevention Studies in p53-Deficient Mice

National Cancer Institute, Bethesda, Maryland 20892

Susan N. Perkins

National Cancer Institute, Bethesda, Maryland 20892

Lawrence A. Donehower

Baylor College of Medicine, Houston, Texas 77030

Barbara J. Davis

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

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Toxicologic Pathology, Vol. 29, No. 1, 137-141 (2001)
DOI: 10.1080/019262301301418946


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Hursting, S. D. Articles by Davis, B. J. Search for Related Content PubMed PubMed Citation Articles by Hursting, S. D. Articles by Davis, B. J. Pubmed/NCBI databases Medline Plus Health Information Cancer Social Bookmarking                         What's this?