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Modulation by Dietary Vitamin E of I-Compounds (Putative Indigenous DNA Modifications) in Rat Liver and Kidney^1,2,

Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030 ^* Department of Experimental Pediatrics, University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030

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 -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.

KEY WORDS: • vitamin E • DNA modification • I-compounds • ³²P-postlabeling • rats

¹ This work was supported by National Cancer Institute grants CA 35363 (to Y.-M. W.) and CA 32157 (to K. R.).

² Presented in part at the 79th Annual Meeting of the American Association for Cancer Research, New Orleans, LA. Li, D., Wang, Y.-M., Nath, R., Parekh, S. & Randerath, K. (1988) Vitamin E effects on age-dependent DNA modifications (I-compounds) in rat liver and kidney. Proc. Am. Assoc. Cancer Res. 29: 146.

³ To whom reprint requests should be sent.

Manuscript received 23 February 1990. Revision accepted 10 July 1990.

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