| First Author | Hursting SD | Year | 1994 |
| Journal | Proc Natl Acad Sci U S A | Volume | 91 |
| Issue | 15 | Pages | 7036-40 |
| PubMed ID | 8041741 | Mgi Jnum | J:97286 |
| Mgi Id | MGI:3575082 | Doi | 10.1073/pnas.91.15.7036 |
| Citation | Hursting SD, et al. (1994) Calorie restriction delays spontaneous tumorigenesis in p53-knockout transgenic mice. Proc Natl Acad Sci U S A 91(15):7036-40 |
| abstractText | Transgenic mice with both alleles of the p53 tumor suppressor gene (frequently mutated in human tumors) knocked out by gene targeting provide a potentially useful tumorigenesis model because these mice rapidly develop spontaneous tumors. To determine whether tumorigenesis in p53-knockout mice is sensitive to experimental manipulation, tumor development in response to calorie restriction (CR; a potent inhibitor of rodent tumors) was evaluated. Tumor development was monitored for 48 weeks in male nullizygous p53-knockout and wild-type littermate mice (28-30 per treatment group) fed ad libitum (AL) or restricted to 60% of AL carbohydrate calorie intake. CR:p53-knockout mice (median survival = 25 weeks) experienced a delay in tumor onset and subsequent mortality (P = 0.0002) relative to AL:p53-knockout mice (median survival = 16 weeks). Tumor development and mortality in wild-type littermates on either diet treatment were < 4% through 48 weeks. Cell cycle analyses were performed on splenocytes from p53-knockout mice and wild-type littermates after 4 weeks of AL feeding or CR (5 per group). The percentage of splenocytes in S phase of the cell cycle was 3-fold higher for p53-knockout mice than wild-type mice (P < 0.001), and CR reduced the percentage of S-phase splenocytes in both p53-knockout and wild-type mice (P = 0.012). These data demonstrate that tumor development in p53-knockout mice genetically predisposed to tumors can be delayed by CR (possibly via cell cycle modulation) and suggest that these mice provide a very useful model of spontaneous tumorigenesis. |
