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Changes in Selenium and Antioxidant Status during DMBA-Induced Mammary Carcinogenesis in Rats^1,2,

Mary R. L'Abbé^*,, Peter W. F. Fischer^*, and Eduardo R. Chavez

^* Nutrition Research Division, Food Directorate, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario K1A 0L2 Department of Animal Science, Macdonald College of McGill University, Ste. Anne de Bellevue, Quebec H9X 1C0, Canada

Female weanling Sprague-Dawley rats were used to examine the changes that occurred in selenium and antioxidant status during the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. Animals were fed an AIN-76 diet, modified to contain 20% fat (3:1 wt/wt, lard:corn oil) and 0.1, 0.035, 0.1, 1.0, 2.0 or 4.0 mg Se/kg diet. At wk 5, rats in groups 2–6 were administered by intragastric tube 4.32 mg of DMBA dissolved in corn oil. Control rats received corn oil only. A blood sample was removed from the tail vein and analyzed for selenium-dependent glutathione peroxidase (SeGSHPx) and superoxide dismutase (SOD) activity at wk 5, and every 4 wk until wk 25. At the end of the experiment, rats were classified by tumor status, and each diet group was subdivided into two groups: those rats remaining free of tumors for 25 wk and those with tumors. DMBA treatment caused an initial decrease in erythrocyte SeGSHPx and SOD activity compared to untreated control rats. SeGSHPx activity in rats with tumors remained lower than controls, while SeGSHPX activity increased in rats with no tumors. These changes, however, were not associated with any changes in lipid peroxidation.

KEY WORDS: • selenium • cancer • glutathione peroxidase • superoxide dismutase • lipid peroxidation • rat • 7,12-dimethylbenz(a)anthracene

¹ Publication No. 276 of the Bureau of Nutritional Sciences.

² Presented in part at the 29th Annual Meeting of the Canadian Federation of Biological Societies, Guelph, Ontario, June 16–20, 1986: Can. Fed. Biol. Soc. Proc. 29: 103 (abs. PA-99).

Manuscript received 14 June 1988. Revision accepted 9 February 1989.