High dietary iron enhances oxidative stress in liver but does not increase aberrant crypt foci development in rats with low vitamin E status.

The purpose of this study was to examine the effects of high-iron and low-vitamin E diets on lipid peroxidation and aberrant crypt foci (ACF) development in rats. In a 2 x 2 x 2 factorial design, male Sprague-Dawley rats were fed 45 or 450 mg Fe/kg diet (adequate and high iron, respectively) and 15 or 100 IU vitamin E/kg diet (low and adequate vitamin E, respectively) for three weeks, when they received saline or azoxymethane (15 mg/kg for 2 wk). Diets were continued for an additional six weeks. Serum alpha-tocopherol concentrations in rats fed low-vitamin E diets were decreased to 30% of concentrations observed in rats fed adequate-vitamin E diets (p < 0.0001). Also, serum alpha-tocopherol concentrations tended to be lower in rats supplemented with iron (p < 0.08). Lipid peroxidation in liver was significantly elevated by high-iron diets after 3 and 10 weeks of treatment, but lipid peroxidation in colonic mucosa was not altered by dietary iron or vitamin E. The total number of ACF and number of large ACF (> or = 4 aberrant crypts/focus) were not significantly altered by iron or vitamin E intakes. However, the size distribution of ACF was slightly altered, such that iron-supplemented rats had 12% more ACF with two crypts per focus (p < 0.02) than rats fed adequate-iron diets. Our data suggest that high-iron diets enhanced oxidative stress in liver, but not colon, of rats fed low-vitamin E diets. Furthermore, a high-iron diet does not increase the total number of ACF, even when vitamin E status is low.