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Toxicological Sciences 66, 125-130 (2002)
Copyright © 2002 by the Society of Toxicology

MOLECULAR AND GENETIC TOXICOLOGY

Effect of Varying Caloric Restriction Levels on Female Rat Growth and 5-Hydroxymethyl-2'-deoxyuridine in DNA

Zora Djuric*,1, Sherry M. Lewis{dagger}, Ming H. Lu{dagger}, Martha Mayhugh{dagger}, Lilian Naegeli*, Ning Tang{dagger} and Ronald W. Hart{dagger}

* Barbara Ann Karmanos Cancer Institute, Wayne State University, 100 E. Warren, Detroit, Michigan 48118; and {dagger} National Center for Toxicological Research, Jefferson, Arkansas 72079

Caloric restriction has previously been shown to decrease levels of oxidative stress in rats. In this study, we examined the effects of 5 different caloric intake levels on one type of oxidative DNA damage in rat mammary gland, blood, and liver. Animals were fed modified AIN-93G diets to accommodate 10, 20, 30, or 40% calorie restriction (CR), relative to ad libitum (AL) consumption. The intakes of fat, protein, vitamins, and minerals thus remained constant, but total carbohydrate intake decreased. Body weights of the animals at 20 weeks reflected the degree of restriction, but in the first 10 weeks, weight gain in the 10% CR group was not reduced relative to animals fed ad libitum. Levels of 5-hydroxymethyl-2'-deoxyuridine increased with time in mammary gland and nucleated blood cells regardless of CR level, indicating an effect of animal age, despite the fact that the animals were only 7 months old after the 20-week dietary study. In liver, however, there was a trend towards decreased DNA damage levels with time. The effect of diet on levels of 5-hydroxymethyl-2'-deoxyuridine was not statistically significant, indicating no protective effect of restricted dietary carbohydrate. This dietary study differed from previous work in that the modified AIN-93G dietary formulation contains relatively higher levels of fat and vitamins K, E, and B12, and it has certain added trace minerals. This data raises the question of whether the previously reported effects of calorie restriction on preventing oxidative stress in mammary gland are dependent on the type of dietary formulation used.

Key Words: caloric restriction; oxidative stress; DNA damage; 5-hydroxymethyl-2'-deoxyuridine; aging; female rats.


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