title: Cancer prevention studies in p53-deficient mice.
abstract: Future progress in mechanism-based cancer prevention research may be facilitated by animal models displaying specific genetic susceptibilities for cancer, such as mice deficient 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.
authors.affiliation: Office of Preventive Oncology, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Hursting
authors.forename: S N
authors.initials: SN
authors.lastname: Perkins
authors.forename: L A
authors.initials: LA
authors.lastname: Donehower
authors.forename: B J
authors.initials: BJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000517:prevention & control*; D011247:Pregnancy; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53