Our objectives are to determine what role, if any, nitrite and nitroso compounds play in the etiology of human cancer. Toward this end, a number of tools and experimental systems capable of measuring the flux of precursors and the quantity of endogenous synthesis of compounds related to nitroso carcinogens in man have now been developed. Studies will continue on the endogenous synthesis of nitrate and nitrite including the determination of the mechanism of biosynthesis in mammalian tissues. The role that macrophages play in the formation of nitrate and N-nitroso compounds will be explored in detail. Our investigations on dimethylamine will focus on the origin and overall flux of this compound with particular emphasis on its entry into the stomach where it can be nitrosated to form a carcinogen. The endogenous formation of nitrosamines will be studied in humans and experimental animals, and emphasis will be placed on optimizing the use of ascorbic acid to block intragastric nitrosation. A new animal model for intragastric nitrosation will be developed using the ferret, a small carnivore with gastric acidity close to the human. In all of these studies physiological pharmacokinetic parameters will be used to model and describe the behavior of the systems. In the area of carcinogenic precursors the research will stress the chemistry of indoles as potential gastric mutagens and carcinogens. Among potential high-risk foods to be examined are black beans from Costa Rica and salted fish from China. The ultimate health goal of this research is to discover conditions that expose humans to carcinogens and to develop methods for eliminating that exposure.
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