A hypothesis for dietary components as blocking agents of chemical carcinogenesis: Plant phenolics and pyrrole pigments

Abstract

Initiation of chemical carcinogenesis involves the intracellular formation of a highly reactive electrophile that can attack many chemical nucleophiles in the cell, including DNA, a process that seems to be the central mechanism of initiation. Competing chemical nucleophiles in the cell, such as endogenous glutathione, can act as protecting or blocking agents against the attack on DNA. There are chemical substances in our food supply that may act as anticarcinogens or antimutagens by blocking or trapping ultimate-carcinogen electrophiles in a nucleophilic chemical reaction, to form innocuous products. A continuous input of these substances could serve as an additional buffer against DNA damage, supplementing the natural systems qualitatively and quantitatively. Certain plant phenolics can be effective inhibitors of chemical mutagens and/or carcinogens. Certain tetrapyrroles and porphyrins, both plant and animal, can also act as blocking agents. Both plant phenolics and porphyrins are primarily active against aromatic carcinogens. They are unlikely to be effective as blocking agents against nonaromatic carcinogens, or those with no aromatic groups in close proximity to the ultimate-carcinogen electrophilic group.