SYNERGISTIC EFFECT OF VITAMIN-E AND SELENIUM IN THE CHEMOPREVENTION OF MAMMARY CARCINOGENESIS IN RATS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (11) , 5335-5341
Abstract
Vitamin E, although ineffective by itself, was able to potentiate the ability of Se to inhibit the development of mammary tumors induced by dimethylbenz[a]anthracene (DMBA) in rats. Animals were maintained on a high-polyunsaturated fat (20% corn oil) diet in order to increase the degree of oxidant stress; additional Se and/or vitamin E were present at a concentration of 2.5 and 1000 mg/kg of diet, respectively. Vitamin E facilitated the anticarcinogenic action of Se only when it was present during the proliferative phase. DMBA resulted in an acute but modest increase in lipid peroxidation at 24 h after carcinogen treatment. This perturbation was transient. The responses in a target tissue (mammary fat pad) and a non-target tissue (liver) suggest that DMBA may have a differential effect on the degree of oxidant stress. The antagonistic effect of Se and vitamin E in suppressing lipid peroxidation was then evaluated. Although vitamin E is a more effective antioxidant than Se, systemic suppression of lipid peroxidation by vitamin E subsequent to a carcinogenic insult is not sufficient to inhibit tumor formation. Vitamin E supplementation increases significantly the microsomal hydroperoxidase activity. It is unclear what role, if any, this enzyme plays in the synergistic effect of vitamin E and Se in tumorigenesis inhibition. The anticarcinogenic action of high levels of Se is not related to its biochemical function in the regulation of the Se-dependent glutathione peroxidase. The explanation for this is that the enzyme is already operating at near maximal capacity under normal physiological conditions. Vitamin E may be able to provide a more favorable climate against oxidant stress, thereby potentiating the action of Se via some other mechanism.