CALORIE RESTRICTION INDUCES A P53-INDEPENDENT DELAY OF SPONTANEOUS CARCINOGENESIS IN P53-DEFICIENT AND WILD-TYPE MICE

We reported previously that calorie restriction (CR) delays spontaneou s carcinogenesis in p53-deficient (p53(-/-)) mice, suggesting that CR modulates carcinogenesis by p53-independent mechanisms, To further eva luate the role of p53, we monitored tumor development in p53(-/-) and wild-type (p53(+/+)) mice fed ad libitum (AL) or a CR regimen (60% of AL calorie intake), CR delayed tumor mortality in p53(-/-) and p53(+/) mice (mean time to death, 169 and 648 days, respectively) relative t o AL feeding (104 and 470 days). The estimated age-specific cancer dea th rate AL:CR ratios were 4.3 for p53(-/-) mice and 4.4 for p53(+/+) m ice, Thus, despite the accelerated onset of carcinogenesis in p53(-/-) mice, the tumor-delaying effect of CR was similar in the two genotype s.