[Heterocyclic aromatic amines, food-derived mutagens: metabolism and relevance to cancer susceptibility].

It is estimated that diet contributes to as much as one-third of cancer incidents. Heterocyclic aromatic amines (HCAs) are well-known mutagens/carcinogens found in thermal-processed meat and fish. HCAs require metabolic activation to exert their carcinogenic potential. First step in HCAs activation--the generation of N-hydroxy-HCA derivatives--is catalyzed by cytochrome P450, mainly isoenzyme CYP1A2. Further activation is carried out by N-acetyltransferases and sulfotransferases, which catalyze esterification of N-hydroxy-HCAs. The products of these reactions are highly genotoxic, capable of direct interaction with DNA by adduct formation. HCA-DNA adducts may cause errors in DNA replication and the generation of mutations, which, when not repaired, may contribute to cancer development. On the other hand, among enzymes involved in HCAs detoxication, UDP-glucuronosyltransferases and glutathione S-transferases can be mentioned. Balance between activation and detoxication processes of HCAs, together with genetically determined differences in HCA metabolism are crucial for the assessment of HCA-dependent cancer risk among individuals.