Chemistry of carcinogenic and mutagenic metabolites of heterocyclic aromatic amines

Ester derivatives of the hydroxylamine metabolic oxidation products of heterocyclic amines (HCAs) are the ultimate mutagenic and carcinogenic compounds derived from this ubiquitous class of chemical carcinogens that are produced during the cooking of protein-containing foods. Considerable work has been done on the mechanism of formation of the HCAs during cooking processes, their detection at ppb levels in food products, the metabolism of the HCAs and the detection and characterization of DNA adducts of the HCA metabolites, but until recently very little work had been done to characterize the chemistry of the carcinogenic/mutagenic metabolites themselves. This paper reviews our recent work on the chemistry of model carcinogens from this class. The kinetics of their decomposition in aqueous solution, identification of reaction products and the characterization of the reactivity and selectivity of heterocyclic nitrenium ions generated during their reactions are presented. The implications of these results with respect to mutagenicity and carcinogenicity are discussed. Copyright (C) 2004 John Wiley Sons, Ltd.