Nitrosamide carcinogenesis: nitrosation of amide linkages and facile decomposition of resulting nitrosamides

Abstract

Nitrite ions interact readily with N-methylacetamide and N-acetylglycine in aqueous buffer solution of pH less than 4 to give the transient nitrosamides, N-nitroso-N-methylacetamide and N-nitroso-N-acetylglycine. These nitrosamides could not be isolated under these conditions because they decompose rapidly, as demonstrated by ultra-violet spectroscopic traces. The gas chromatographic identification of the products indicates that diazo esters and diazoalkanes are the intermediates in these decompositions. The kinetic analysis of the nitrosation in buffered solution shows that the rate constants are proportional to the hydrogen ion concentration in the pH less than 4 range. Evidence in support of the participation of a carboxylate group in the nitrosation of N-acetylglycine is discussed. Possible implications of the presence of nitrite in carcinogenesis in digestive tracts are discussed on the basis of facile formation and decomposition of nitrosamides and the intermediacy of diazo compounds.