An overview of the formation mechanisms of endogenous and exogenous N-nitrosamines in human diets.

There are two formation routes of dietary N-nitrosamines: exogenous and endogenous formation. The formation of N-nitrosamines from either source requires precursors with a dialkylamine functional group and a nitrosating agent. Precursors are supplied primarily by amine-rich foods and nitrosating agents are nitrite or its reaction products (N2O3 and NO+). Unprocessed fresh foods initially contain zero or only trace amounts of N-nitrosamines while significant amounts of N-nitrosamines can be generated during certain types of food processing. Cooking methods, pH, additives, and storage conditions can affect the formation of N-nitrosamines in foods. We analysed the formation mechanisms/pathways of the three most frequently detected N-nitrosamines in processed meats. Formation of endogenous N-nitrosamines is likely to be greater than that of exogenous N-nitrosamines. Nitrosating agents involved in the formation of endogenous N-nitrosamines are formed from nitrate in vegetables via the nitrate-nitrite-NO cycle. N-nitrosamines are produced in the human stomach and intestine but their formation mechanisms differ. We analysed the mechanism/pathway for the formation of N-nitrosotryptophan from tryptophan in the stomach. The formation of N-nitrosamines in the intestine includes both chemical and microbiological mechanisms. In addition to N-nitrosation, S-nitrosation also occurs in the human body. There is a competitive relationship between the two reactions, and S-nitrosation is more likely to occur in the healthy human body. This paper reviews the mechanisms and factors influencing the formation of exogenous and endogenous dietary N-nitrosamines, which illustrate the importance of microbial-mediated N-nitrosamine formation and the production of endogenous N-nitrosamines.