© 2004 by Oxford University Press
© 2004 Oxford University Press
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Dose-Dependent Effects of Dietary 
- and 
-Tocopherols on Genetic Instability in Mouse Mutatect Tumors
Affiliations of authors: Ottawa Regional Cancer Centre and the Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ontario, Canada (CCYS, HCB); Institute for Biological Sciences, National Research Council, Ottawa, Ontario, Canada (ASH); Nutrition Research Division, Health Canada, Ontario, Canada (NH); Division of Nutritional Sciences, Cornell University, Ithaca, NY (JES, RSP).
Correspondence to: H. Chaim Birnboim, MD, MSc, Ottawa Regional Cancer Centre, 503 Smyth Rd., Ottawa, ON, Canada K1H 1C4 (e-mail: birnboim{at}uottawa.ca)
Vitamin E in foodstuffs is a mixture of tocopherols. In mouse Mutatect tumors, a model designed to detect DNA mutations, the hypoxanthine phosphoribosyltransferase (Hprt) gene mutation frequency is associated with the number of tumor-infiltrating neutrophils and both are markedly decreased in mice fed high levels of 
-tocopherol. Dietary -tocopherol is also associated with a decrease in neutrophil-associated loss of an interleukin 8 (IL-8)-expressing transgene in this tumor model. We examined Hprt gene mutation frequency (expressed as the number of 6-thioguanine–resistant colonies per 105 clonable tumor cells), IL-8 transgene loss, and myeloperoxidase activity (an indirect measure of neutrophil number) in tumors from Mutatect mice fed diets supplemented with various concentrations of D--tocopherol acetate and/or D-
-tocopherol acetate or neither tocopherol for 4 weeks. Hprt gene mutation frequency and myeloperoxidase activity were statistically significantly lower in tumor cells from mice fed -tocopherol at 50 or 100 mg/kg body weight per day than in tumor cells from mice fed 0 mg/kg body weight per day -tocopherol (P<.001 for each comparison). IL-8 transgene loss occurred in 28 of 28 tumors (100%; 95% confidence interval [CI] = 86% to 100%) from mice fed -tocopherol at 50 mg or less/kg body weight per day and seven of 18 tumors (39%; 95% CI = 24% to 54%) from mice fed 100 mg/kg body weight per day (P<.001, Fisher’s exact test, referent groups [pooled] 0, 25, and 50 mg/kg). -Tocopherol had no detectable effect on any of the three endpoints. Thus, dietary -tocopherol decreases two forms of genetic instability in a dose-dependent manner in this experimental tumor model.
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