Cancer-protective factors in fruits and vegetables: biochemical and biological background.

Cancer-protective factors are present in several fruits, vegetables and commonly used spices and herbs. They can be divided into several different groups, based on their chemical structure, e.g. polyphenols, thiols, carotenoids and retinoids, carbohydrates, trace metals, terpenes, tocopherols and degradation products of glucosinolates (i.e. isothiocyanates, indoles and dithiothiols) and others. Among each of these groups of compounds are substances, which may exert their cancer-protective action by more than one biochemical mechanism. The biochemical processes of carcinogenesis are still not known in detail and probably varies with the cancer disease in question. Accordingly, the description of the biochemical backgrounds for the actions of cancer-protective factors must be based on a simplified model of the process of carcinogenesis. The model used in this presentation is a generalised initiation-promotion-conversion model, in which initiators are thought to be directly or indirectly genotoxic, promoters are visualised as substances capable of inferring a growth advantage on initiated cells and converters are believed to be genotoxic, e.g. mutagens, clastogens, recombinogens or the like. Experimental evidence for the mechanisms of action of cancer-protective agents in fruits and vegetables that protect against initiation include the scavenging effects of polyphenols on activated mutagens and carcinogens, the quenching of singlet oxygen and radicals by carotenoids, the antioxidant effects of many compounds including ascorbic acid and polyphenols, the inhibition of activating enzymes by some flavonols and tannins, the induction of oxidation- and of conjugation (protective) enzymes by indoles, isothiocyanates and dithiothiones, the shielding of sensitive structures by some polyphenols and the stimulation of DNA-repair exerted by sulphur-containing compounds. Mechanisms at the biochemical level in anti-promotion include the antioxidant effects of carotenoids and the membrane stabilizing effects reported with polyphenols, the inhibition of proteases caused by compounds from soybeans, the stimulation of immune responses seen with carotenoids and ascorbic acid and the inhibition of ornithine decarboxylase by polyphenols and carotenoids. A few inhibitors of conversion have been identified experimentally, and it can be argued on a theoretical basis, that many inhibitors of initiation should also be efficient against conversion. The mechanisms of anticarcinogenic substances in fruits and vegetables are discussed in the light of cancer prevention and inhibition.