Dose-dependent effects of dietary α- and γ-tocopherols on genetic instability in mouse mutatect tumors

Abstract

Vitamin E in foodstuffs is a mixture of tocopherols. In mouse Mutated 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 α-tocopherol. Dietary α-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-α-tocopherol acetate and/or D-γ -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 α-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 α-tocopherol (P