Mode of action of selenium inhibition of 7,12-dimethylbenz[a]anthracene-induced mouse mammary tumorigenesis

Abstract

Possible mechanisms for the inhibitory effect of selenium on mouse mammary gland tumorigenesis were evaluated in two different mouse models, in 7,12-dimethylbenz[a]anthracene [(DMBA) CAS:57-97-6]treated and hormonally stimulated mammary glands with two dietary levels of Se (0.2 and 2.0 ppm). In (C57BL X DBA/2f)F1 (BD2F1) and BALB/c strains of female mice, Se at 2.0 ppm decreased mammary tumor incidences by 36 and 68%, respectively. Selenium-dependent glutathione peroxidase (GSH-Px) activity in the mammary glands of BD2F1 female mice decreased at 6 months of age and then increased to the highest levels at 9 months of age. Mammary glands from DMBA-treated mice had lower GSH-Px activity than those from control mice. The increase of dietary Se to 2.0 ppm did not overcome this DMBA effect. These results indicate that GSH-Px activity does not correlate with the tumorigenic inhibitory effects of Se. In the hormonally stimulated mammary gland, increasing dietary Se to 2.0 ppm increased GSH-Px activity threefold and decreased mammary-gland-membrane-localized lipid peroxidation by 16%. In vitro peroxidation of hormonally stimulated mammary glands was inversely proportional to the level of GSH present in the incubation mixture. The marginal decrease in lipid peroxidation found in the mammary glands exposed to 2.0 ppm Se could not explain the inhibitory effect of Se on tumorigenesis.