Abstract
B224
Chronic calorie restriction (CCR) prevents cancer of the breast and prostate in rodent models. For example, in Lobund-Wistar rats restricted by 30% prostate tumors developed at lower rates (Cancer 65:686, 1989), and these rats had increased survival compared to ad libitum fed rats (J Gerontol 45:B52, 1990). Recently, intermittent caloric restriction (ICR) was reported to be more protecive than CCR in two transgenic mouse models that develop mammary tumors (CEBP 11:836, 2002; Nutr Cancer 44:161, 2002), i.e., lower incidences and delayed latency of mammary tumors were detected in ICR mice in comparison to ad libitum fed, as well as to CCR mice. Here, we used the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse to determine how similar caloric restriction protocols, ICR vs CCR, would offer protection against prostate cancer. Male C57BL6 TRAMP mice were assigned to 1) ad libitum (AL, free access to AIN-93M diet), 2) ICR (2-wk of 50% caloric restriction using AIN-93M diet with 2x protein, fat, vitamins, and minerals followed by 2-wk of 100% AL consumption of AIN-93M for each corresponding 2-wk), 3) CCR (fed a diet mixture to match calorie and nutritent intake for each four week ICR cycle ~75% of AL consumption) groups. Protocols were initiated at 7 wk of age and mice followed until disease burden necessitated euthanasia or mice reached terminal endpoints of 48 (last of 11 restrictions) or 50 (last of 11 refeedings) wk of age. Body weights fluctuated in response to calorie intake during the study and were significantly different among the three cohorts (p < 0.0001). Final body weights of AL mice were the heaviest followed by ICR-refed, while CCR and ICR-restricted mice weighed the least. Time to tumor detection was significantly different among the three groups (log rank χ2 = 8.736, 2 degrees of freedom, p = 0.0127); occurring at median ages of 33, 35 and 38 wk of age for AL, CCR and ICR mice, respectively. There was no statistical difference for age of prostate tumor detection between AL and CCR mice, while ICR mice were significantly older than both AL (p = 0.0051) and CCR (p = 0.03) mice. Tumor grade was not different among the groups. A significant difference in survival time was also found among the three groups (log rank χ2 = 12.498, 2 degrees of freedom, p = 0.009). ICR mice had the longest median survival compared to CCR and AL mice, 46, 40 and 41 wk of age, respectively. Forty percent of ICR mice reached their designated terminal end point compared to 27% and 10% for CCR and AL, respectively. Results from this study indicate that mode of caloric restriction impacts both time to tumor detection and survival in TRAMP mice with intermittent restriction providing a greater protective effect compared to chronic restriction. (Support: DAMD17-03-1-0258 and Hormel Foundation)
[Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006]