Mechanisms by which the chemoprevention of mammary carcinogenesis by selenium is affected will be examined and long term carcinogenesis experiments to study the activity of selenium as an inhibitor of dietary induced tumor promotion will be conducted. The reductive metabolism of selenium by the mammary gland from selenite to selenide will be investigated as the basis for its chemopreventive activity during post-initiation events of 1-methyl-1-nitrosourea (MNU)-induced mammary carcinogenesis. Primary consideration will be given to selenite-mediated changes in tissue concentrations of S-adenosylmethionine, putrescine, spermidine, and spermine as they relate to proliferative activity of the mammary gland and tumor occurrence. The production of volatile metabolites of selenium from selenite by subcellular fractions of mammary epithelial cells and by mammary glands in culture will be examined and the urinary and volatile loss of selenium by animals fed varying concentrations of dietary selenite measured. Radiochemical and spectrometric techniques will be employed for these experiments. Polyamines will be measured by fluorescence following thin layer chromatography and the proliferative activity of the mammary gland will be assessed autoradiographically. Effects of selenite metabolism will be investigated both in vivo and in culture. In the carcinogenesis studies the antipromotor activity of selenium against mammamry carcinogenesis will be determined in animals given a subcarcinogenic initiating dose of MNU with tumor occurrence being promoted by a diet containing 20% fat in a highly unsaturated form. The proposed work represents the investigation of the role of one of many aspects of diet and nutrition which may influence the carcinogenic process. Ultimately this research could lead to the development of dietary and/or therapeutic recommendations which enhance our ability to prevent and control cancer of the breast.
| Thompson, H J; Herbst, E J; Meeker, L D (1986) Chemoprevention of mammary carcinogenesis: a comparative review of the efficacy of a polyamine antimetabolite, retinoids, and selenium. J Natl Cancer Inst 77:595-8 |
| Meeker, L D; Thompson, H J (1985) A multi-path theory of chemical carcinogenesis in the rat mammary gland. Prog Clin Biol Res 172A:379-88 |
