Antimutagens, anticarcinogens, and effective worldwide cancer prevention.

Cancer is the eventual outcome of the transformation of normal cells by DNA-reactive, genotoxic carcinogens and the growth promotion of mutated cells by enhancing factors. It is important to discriminate between genotoxic carcinogens and nongenotoxic chemicals because their mechanisms of action are quite distinct. Their dose-response curves, reversibility, and organ- and species-specificity are also quite distinct. Thus, the mode of action of agents involved in cancer causation and development needs careful analysis. Genotoxic carcinogens are mutagenic, form DNA adducts, and lead to the formation of hydroxy radicals and inappropriate peroxidation reactions that the antioxidants in vegetables, fruits, and tea can effectively decrease. About 35% of known cancers are associated with tobacco use and about 55% with inappropriate nutritional habits. Cancer induction can be decreased by (1) avoiding the formation of carcinogens, (2) reducing their metabolic activation, or (3) increasing their detoxification. Nutritional factors play a major role in cancer prevention. Vegetables, fruits, and the beverage, tea, provide select means to prevent activation of carcinogens or to increase their detoxification. Salting and pickling of certain foods generate direct-acting mutagens and carcinogens that affect the stomach and probably the esophagus. Thus, controlling salt use and increasing vegetable and fruit intake can prevent these diseases. Frying and broiling protein foods generate heterocyclic amines that affect the colon, breast, prostate, and pancreas, and their formation is decreased by antioxidants. Heterocyclic amines are converted to reactive components by specific cytochrome P450 enzymes and N-acetyltransferases. The tobacco-specific nitrosamines and polycyclic aromatic hydrocarbons undergo specific activation and detoxification processes. These reactions are controlled by antioxidants such as quercetin in vegetables, polyphenols in tea, genistein and daidzin in soy, sulforaphane in broccoli, and 3-methylindole and isothiocyanates in such protective foods. In the Western world, the type and amount of fat play a critical role that operates through specific promoting mechanisms to modify the action of genotoxic carcinogens. In most Western countries where mixed fats and oils are consumed, the total amount of fat at 35 to 40% of calories acts as a powerful promoter. On the other hand, in Italy and Greece, where the monounsaturated oil, olive oil, is used almost exclusively without promoting effect, little enhancement by fat is observed. Also, in the Mediterranean region, meats, mainly veal, are not browned to the point of generating heterocyclic amines. Wheat bran fiber increases stool bulk and eliminates carcinogens and the promoters of colon and breast cancers. Thus, the current base of knowledge on the mechanisms of cancer causation provides effective ways of preventing most types of cancer, the definitive means of cancer control.