Abstract

A continuing study of chemopreventive agents has focused on three categories of naturally-occurring compounds that inhibit carcinogen activation and are effective in preventing carcinogen-induced neoplasia when administered at short time intervals prior to carcinogen challenge. The three are: aromatic isothiocyanates found in cruciferous vegetables, monoterpenes from citrus fruits and caraway seed oils, and organosulfur compounds occurring in Allium species. The short time-interval effects could be significant in terms of their impact on responses of humans to carcinogen exposures. The capacity of sodium cyanate, 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 multiphase activity were presented. The first is that these inhibitory substances activate a complex integrated defense mechanism against toxic compounds which entails both blocking and suppressing components. The blocking component is the initial line of defense, 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.