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Carcinogenesis, Vol. 23, No. 5, 817-822, May 2002
© 2002 Oxford University Press

MOLECULAR EPIDEMIOLOGY

Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice

David Berrigan1,2, Susan N. Perkins1,2, Diana C. Haines3 and Stephen D. Hursting1,2,4

1 Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892-7105, USA,
2 Laboratory of Biosystems and Cancer, National Cancer Institute, Bethesda, MD 20892-7105, USA and
3 Pathology/Histotechnology Laboratory, SAIC, NCI-Frederick, Frederick, MD 21702-1201, USA

Abstract

Heterozygous p53-deficient (p53+/–) mice, a potential model for human Li-Fraumeni Syndrome, have one functional allele of the p53 tumor suppressor gene. These mice are prone to spontaneous neoplasms, most commonly sarcoma and lymphoma; the median time to death of p53+/– mice is 18 months. We have shown previously that juvenile-onset calorie restriction (CR) to 60% of ad libitum (AL) intake delays tumor development in young p53-null (–/–) mice by a p53-independent and insulin-like growth factor 1 (IGF-1)-related mechanism. To determine whether CR is effective when started in adult p53-deficient mice, and to compare chronic CR with an intermittent fasting regimen, male p53+/– mice (7–10 months old, 31–32 mice/group) were randomly assigned to the following regimens: (i) AL (AIN-76A diet), (ii) CR to 60% of AL intake or (iii) 1 day/week fast. Food availability on non-fasting days was controlled to prevent compensatory over feeding. Relative to the AL group, CR significantly delayed (P =; 0.001) the onset of tumors in adult mice, whereas the 1 day/week fast caused a moderate delay (P =; 0.039). Substantial variation in longevity and maximum body weight within treatments was not correlated with variation in growth characteristics of individual mice. In a separate group of p53+/– mice treated for 4 weeks (n =; five mice per treatment), plasma IGF-1 levels in CR versus AL mice were reduced by 20% (P < 0.01) and leptin levels were reduced by 71% (P < 0.01); fasted mice had intermediate levels of leptin and IGF-1. Our findings that CR or a 1 day/week fast suppressed carcinogenesis—even when started late in life in mice predestined to develop tumors due to decreased p53 gene dosage—support efforts to identify suitable interventions influencing energy balance in humans as a tool for cancer prevention.


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