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Vitamin E Inhibits Apoptosis, DNA Modification, and Cancer Incidence Induced by Iron-mediated Peroxidation in Wistar Rat Kidney¹

Department of Pathology, Okayama University Medical School, Okayama 700 [D. Z., S. O.], and Department of Environmental Oncology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807 [R. Y., H. K.], Japan; and Department of Pathology, First People's Hospital of Shanghai, Shanghai 200080 [Y. Y.], and Division of Renal Diseases Research, The Shanghai University of Chinese Traditional Medicine, Shanghai 200080 [P. Z.], The People's Republic of China

We have developed an experimental model of iron-induced oxidative nephrotoxicity and renal cancer. Using this model, the effect of vitamin E, a known antioxidant, was investigated. Three-week-old male Wistar rats were fed with vitamin E-sufficient (control) and vitamin E-supplemented diets throughout the experiment. After 1 month of feeding, iron-induced tissue lipid peroxidation, apoptosis, and formation of 8-hydroxydeoxyguanosine, a known DNA oxidative modification, were observed by cold Schiff staining, in situ labeling method (staining by terminal deoxynucleotidyl transferase-mediated nick end labeling), and high-performance liquid chromatography with electrochemical detection system, respectively, in the groups of rats treated with ferric nitrilotriacetate (Fe-NTA; Fe, 10 mg/kg body weight). For the vitamin E intervention study on Fe-NTA-induced renal carcinogenesis, two groups of rats fed vitamin E-sufficient and vitamin E-supplemented diets (30 and 20 rats, respectively) were treated with Fe-NTA (Fe, 7.5 mg/kg body weight once or twice a week) i.p. for 3 months and observed for 9 additional months. Five of the vitamin E-sufficient rats died during the first 3-month period. The results showed that vitamin E could inhibit tissue lipid peroxidation, apoptosis, 8-hydroxydeoxyguanosine formation, and the development of cancer [11 of 25 rats (44%) for vitamin E-sufficient versus 1 of 20 rats (5%) for vitamin E-supplemented rats, respectively]. These studies strongly suggest that in Fe-NTA-induced renal cancer, as with certain other types of cancer, oxidative stress plays an important role in carcinogenesis, and an antioxidant is an effective chemopreventive measure.

¹ This work was supported by a grant-in-aid from the Ministry of Health and Welfare, Japan.

² To whom requests for reprints should be addressed.

Received 12/13/96. Accepted 4/22/97.

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