CARCINOGENESIS: NITROSAMINE FORMATION AND INHIBITION

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The proposed research as a high probability of identifying important chemical features which both predispose and serve to block or inhibit the rapid formation of carcinogenic nitrosamines from certain nitrogen compounds both in vivo and in the environment. There are many gaps in our knowledge of the molecular and other chemical factors which lead to rapid or significant nitrosamine formation. It is not know, for example, how nitrosamines are formed in cosmetics, shampoos, other toiletry items, metalworking fluids, and tobacco. Endogenous formation of many N-nitroso compounds may go undetected because of their rapid and possible injurious metabolism. We believe that a fundamental understanding of the chemistry of the nitrosation process, particularly as it relates to ternary nitrogen compounds, can lead to methods for eliminating or decreasing exposure to nitrosamines and thereby prevent human cancer. The rapid formation of nitrosamines from ternary nitrogen compounds including tertiary amines containing an electron rich aromatic ring, tertiary amidines, and gem diamines, will be examined with respect to the necessary structural features and the variables of endogenous nitrosation, nitrite level, pH, and - SCN concentration. Several complex drugs and food constituents including reserpine, hexetidine, methaphenaline, amidinocillin and medibazine will be screened for mutagenicity. Pyrroles and polymers containing pyrroles will be examined for their ability to block nitrosamine formation. Ester mediated nitrosation, a reaction discovered through this research and possibly responsible for inadvertent nitrosamine formation in commercial samples, will be further elucidated.