Nitrosation of dietary precursors.
The diet contains a large number of constituents which can be nitrosated in the gastrointestinal tract (especially in the stomach) to potentially carcinogenic nitroso compounds (NOC). The nitrosation of food mixtures has been investigated with a number of assays, such as chemical analysis or detection of alkylating potential, mutagenicity and carcinogenicity. Relatively good information is available on the formation of stable nitrosamines using high nitrite concentrations. Little is known, however, about the formation of chemically unstable NOC at low nitrite concentration and their genotoxicity in target cells. A comparison of the precursor classes, alkylamines, aromatic amines, amino acids, amides and peptides, ureas and guanidines, reveals a vast range, both with respect to daily intake (10(5)-fold) and nitrosation rate (10(4)-fold both for 1st and 2nd order nitrite dependence). A total span of 10(8) results for the relative yield of NOC in the stomach. The endogenous NOC burden from dietary ureas and aromatic amines may represent as large a hazard as the intake of preformed NOC. Recent evidence also indicates that heterocyclic amines and phenols must be considered and that the half-life of nitrosated alpha-amino acids can be much longer than that of nitrosated primary alkylamines. In these classes, more information should be collected on dietary concentrations, on the nitrosation under realistic conditions and on the genotoxicity in stomach lining cells. Within a chemical precursor class, a wide range is seen with respect to alkylating potency. It cannot, therefore, be excluded that individual precursors within the top ranking classes might become more important than single preformed NOC. Not considered in the above analysis but probably just as important for a risk evaluation in a population is the knowledge of the nitrosation conditions and target cell susceptibility in individuals.
Shephard
S E
SE
Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach.
Lutz
W K
WK
D000818:Animals; D015197:Carcinogenicity Tests; D004247:DNA / Q000378:metabolism; D004032:Diet; D005504:Food Analysis; D006801:Humans; D009152:Mutagenicity Tests; D015538:Nitrosation; D009603:Nitroso Compounds / Q000032:analysis / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats
D009603:Nitroso Compounds; D004247:DNA