Modulation of heterocyclic amine-induced mutagenicity and carcinogenicity: an 'A-to-Z' guide to chemopreventive agents, promoters, and transgenic models.

A landmark report by Widmark in 1939 describing "cancer-producing substances in roasted food", and the seminal work of Sugimura and colleagues in the 1970s on the isolation of potent mutagens from cooked meat and fish stimulated a major international effort on the study of heterocyclic amines and their modulators. The latter term is used in its broadest context to mean agents or conditions that positively or negatively influence the mutagenic or carcinogenic activities of heterocyclic amines in vitro or in vivo. An 'A-to-Z' list of these modulators includes well over 150 natural or synthetic phytochemicals, micronutrients and antioxidants, as well as several large chemical classes (polyphenols, flavones, retinoids, porphyrins), food fractions, and food preparation methods. In many cases, the findings reported in the literature can be regarded as descriptive, but for a number of specific agents there is sufficient evidence to glean some understanding of the inhibitory or promotional mechanisms of action. These mechanisms can be divided into 11 separate sub-categories, arranged within a general classification scheme that encompasses such terms as 'blocking agents', 'suppressing agents', 'desmutagens', 'bioantimutagens', 'interceptor molecules' and 'tumor promoters'. In addition, new research directions, most notably during the past 2-3 years or so, have led to the use of novel dosing protocols and unique animal models (including transgenic species) that provide insight into exposure conditions and genetic background as modulators of heterocyclic amine activity in vitro and in vivo. Overall, the more than 250 citations on the subject give ample evidence of the growing interest in modulators of heterocyclic amine carcinogenesis and mutagenesis, and their possible importance in determining human cancer risk in defined populations.