Heterocyclic Aromatic Amines Heterocomplexation with Biologically Active Aromatic Compounds and Its Possible Role in Chemoprevention

Food-borne heterocyclic aromatic amines (HCAs) are known mutagens and carcinogens present especially in Western population diet, which contains large amount of meat and its products. HCAs are capable of interacting with DNA directly through the formation of covalent adducts, however this process requires biological activation in liver, mainly by cytochrome P450 enzymes. This process may produce mutations and in consequence may contribute to the development of cancer. However, there are many studies showing that several biologically active aromatic compounds (BACs) may protect against genotoxic effects of HCAs. Direct interactions and noncovalent heterocomplexes formation may be one of the most important mechanisms of such protection. This work describes several BACs present in human diet, which are capable of molecular complexes formation with HCAs and protect cells as well as whole organisms against HCAs action. 1. Introduction Several human mutagens and carcinogens belong to aromatics. Polycyclic hydrocarbons (PAHs), aflatoxins, ethidium bromide, acridine dyes such as ICR170 and ICR191, anticancer drugs: daunomycin, doxorubicin, and mitoxantrone, and food-derived heterocyclic aromatic amines (HCAs) can serve as examples. Among them, vast attention is paid to HCAs, which might be responsible for the increase in gastrointestinal tract cancers, observed particularly in Western diet populations with high meat intake (Figure 1). Figure 1: Examples of heterocyclic aromatic amines (HCAs) chemical structures. IQ: 2-amino-3-methylimidazo[4,5- f]quinoline; MeIQ: 2-amino-3,4-dimethylomidazo[4,5- f]quinoline; MeIQx: 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline; PhIP: 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine; Trp-P-2: 3-amino-1-methyl-5 H-pyrido[4,3- b]indole; Glu-P-1: 2-amino-6-methyldipyrido[1,2- a: 3′,2′- d]imidazole. The mutagenic activity of thermally processed meat was firstly observed in 1939 [1] and subsequently in the late 1970s [2]. These observations led to the isolation and characterization of a new class of potent food-borne mutagens/carcinogens, heterocyclic aromatic amines (HCAs) [3]. Basing on their structures, HCAs can be divided into two classes [4]. 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ-) type HCAs are produced during heat processing of creatine/creatinine, sugars, and free amino acids mixtures in temperatures below 300°C in the Maillard reaction. The second class, non-IQ-type HCAs, are formed at higher temperatures, above 300°C by pyrolysis of amino acids and proteins. All HCAs have at least one aromatic and one heterocyclic