Effects of selenium on mouse mammary tumorigenesis and glutathione peroxidase activity

Abstract

The effects of supplemental selenium on 7,12-dimethylbenz(a)anthracene (DMBA)-induced and murine mammary tumor virus (MuMTV)-induced mammary tumorigenesis were investigated in BALB/c mice. Selenium (4-10 ppm), administered in the drinking water, inhibited mammary tumor formation in DMBA-treated mice. The higher doses of selenium (7-10 ppm) were tolerated well by the DMBA-treated mice and blocked mammary tumor formation by 80-90%. In addition, selenium at the lowest dose (4 ppm) inhibited the tumor-producing capabilities of a MuMTV-positive preneoplastic nodule outgrowth line by greater than 75%. The inhibition of tumor formation could not be attributed to an alteration in virus expression because there was no qualitative difference in the expression of of MuMTV proteins between selenium-treated and -untreated mice. Additionally, selenium-dependent glutathione peroxidase activity was detectable in normal virgin and preneoplastic mammary tissues of mice raised on a commercial diet and was increased 2-fold by 4 ppm supplemental selenium in the drinking water. These results demonstrate that supplemental selenium is an effective inhibitor of both chemical- and viral-induced mouse mammary tumorigenesis, and secondly, that the neoplastic transformation in, as well as the development of, preneoplastic lesions is sensitive to selenium-mediated inhibition.