Inhibition of carcinogenesis by minor anutrient constituents of the diet.

A continuing study of chemopreventive agents has focused on several categories of naturally occurring compounds that inhibit carcinogen activation and are effective in preventing carcinogen-induced neoplasia when administered at short time-intervals before carcinogen challenge. The inhibitory compounds are: aromatic isothiocyanates found in cruciferous vegetables, monoterpenes present in citrus fruits and caraway-seed oil, and organosulphur compounds occurring in Allium species. Preliminary work indicates that glucobrassicin and indoles existing in cruciferous vegetables also have these attributes. Almost all carcinogens that are consumed in food require metabolic activation. Thus, inhibition of carcinogen activation reactions could be effective against this type of exposure. In addition, three naturally occurring compounds, i.e. phenethyl isothiocyanate, D-limonene and dipropyl sulphide inhibit activation of the tobacco-specific carcinogen NNK, and accordingly may have the capacity to diminish carcinogenic response to exposures to tobacco. The property of cruciferous vegetables, orange oil, benzyl isothiocyanate, and D-limonene, to act as both blocking and suppressing agents has been discussed. Two possible mechanisms for this multi-phase activity were presented. The first is that these inhibitory substances activate a complex integrated defence mechanism against toxic compounds which entails both blocking and suppressing components. The blocking component is the initial line of defence, and the suppressing component constitutes a 'fail-safe' backup to assure that if any of the toxic material attacks cellular constituents, its effects will be nullified. The second possible mechanism considered is that the inhibitors, because of high reactivity, have multiple biological effects that are separate and not part of a single, coordinated response. Inhibitors that have both blocking and suppressing effects could be particularly useful as chemopreventive agents. A simple interim classification of foods in terms of their potential impact on the occurrences of cancer has been proposed.