The Chemical Basis of the Antinitrosating Action of Polyphenolic Cancer Chemopreventive Agents

A regular intake of polyphenolic agents widely found in fruits and vegetables is believed to decrease the incidence of certain forms of cancer, due in part to their ability to act as antinitrosating agents capable of lowering the impact of toxic nitrosation processes and carcinogenic nitrosamine formation within the acidic environment of the stomach. As a result, the study of the interactions between reactive nitrogen species and phenolic antioxidants has emerged as an area of great promise for delineating innovative strategies in cancer chemoprevention. The burst of interest in (poly)phenolic cancer chemopreventive agents of dietary origin is exemplified by the exponential growth of scientific literature on green tea catechins, as well as on hydroxycinnamates, hydroxytyrosol, flavonoids and other phenolic compounds of the Mediterranean diet, currently regarded as a cultural model for dietary improvement. However, as is often the case with rapidly growing fields, most of these advances have not yet been assessed nor properly integrated into a well defined conceptual framework, whereby several aspects of the chemistry underlying their mechanism of action have remained either obscure or have been taken for granted without sufficient experimental support. The objective of this paper is to provide an account of the chemical mechanisms through which polyphenolic compounds of dietary origin may react with nitrite-derived nitrosating species under conditions that model those occurring in the stomach and other acidic biological compartments. The relevance of this chemistry to the actual role of these substances in DNA protection and cancer prevention remains a critical goal for future studies.