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KMID : 0379519900060020167
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한국독성학회지
1990 Volume.6 No. 2 p.167 ~ p.182
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MODULATION OF TOXICITY AND CARCINOGENESIS BY CALORIC RESTRICION
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Allaben, William T.
Chou, Ming W./Pegram, Rex.A./Leakey, Julian/Feuers, Ritchie J./Duffy, Peter H./Turturro, Angelo
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Abstract
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Dietary restriction (caloric restriction) is the only intervention which has been reliably shown to extend the maximum life span of warm-blooded animals and delay the many phenomena associated with aging. It is also one of the most effective modulators of toxicity, especially cancer endpoints. In spite of the known modulator effects of caloric restriction, the biological mechanisms responsible for these effects had not been investigated until recently. The National Center for Toxicological Research (NCTR), in a collaborative effort with the National Institute of Aging (NIA), initiated a project whereby nine (9) combinations of rodent species/strains and diets were fed both restricted and ad libitum. The NIA´s initiative was to identify biomarkers of aging whereas NCTR´s initiative was to identify the biological effects associated with the profound effects caloric restriction has in protecting against both spontaneous (age-related) and chemically-induced toxic endpoints. Independent of sex or species, caloric restriction has similar effects on body temperature, oxygen consumption and CO, production. Caloric restriction also decreased lipid glycolysis and metabolism in rats and mice, which suggest decreased production of metabolites which could lead to fatty acid epoxide formation. The age-associated loss of circadian regulation of intermediate enzymes is also significantly reduced. Moreover, caloric restriction reduced the age-associated feminization of sexually dimorphic liver isozymes. increased several glucocorticoid responsive isozymes. elevated glucagon/insulin ratios, produced less microsomal superoxide and enhanced the capacity for utilizing detoxicat nc metabolic pathways. Calorically restricted rats have less than half the number of aflatoxin (AFB,)-DNA adducts than ad b%tum animals and urinary excretion of AFB, was increased significantly. Finally, DNA repair mechanisms are enhanced :rd rncogene expression is decreased in calorically restricted anirr.
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