Modulation by dietary vitamin E of I-compounds (putative indigenous DNA modifications) in rat liver and kidney

I(indigenous)-compounds are age-related, carcinogen adduct-like, putative indigenous DNA modifications detectable by 32P-postlabeling assay in untreated animals. To investigate the origins of these DNA derivatives, we examined the effects of dietary vitamin E, a natural antioxidant, on I-compounds of rat liver and kidney DNA. Weanling female Sprague-Dawley rats were fed Draper's diets containing 0, 100, 1000, or 10,000 mg/kg alpha-tocopheryl acetate for 6 mo. The DNA from four individual rats of each group was analyzed by a nuclease P1-enhanced version of the 32P-postlabeling assay for DNA adducts. The amount of vitamin E in the liver was measured by high performance liquid chromatography. Rats fed vitamin E-deficient diet (0 mg/kg) showed identical profiles and similar levels of I-compounds as those fed the 100 mg/kg diet. Most I-spots were significantly intensified and one tissue-specific extra spot was found in both liver and kidney DNA of rats fed the 1000 or 10,000 mg/kg vitamin E diet. However, one of the five major I-spots detected in the kidney was weaker in the 1000 and 10,000 mg/kg groups than in the 0 and 100 mg/kg groups. These results show that formation of most I-compounds was not affected by vitamin E-deficient diet, and that long-term feeding of diet containing high levels of vitamin E may cause metabolic alterations leading to an increased formation of DNA-reactive (potentially mutagenic or carcinogenic) electrophiles.