Inhibitors of chemical carcinogens.

A diverse group of compounds inhibit the action of chemical carcinogens when administered prior to and/or simultaneously with the carcinogen. The inhibitors include naturally-occurring constituents of foods as well as synthetic compounds introduced into the environment. Three general mechanisms of inhibition exist. The first, illustrated by disulfiram inhibition of dimethylhydrazine-induced neoplasia of the large bowel, is the direct blocking of enzymatic activation of the carcinogen to its reactive ultimate carcinogenic form. The second mechanism of inhibition entails the stimulation of a coordinated detoxification response which results in increased activity of detoxifying enzymes in the microsomes and also the cytosol. At least two subdivisions of this response occur. One, for which butylated hydroxyanisole is a prototype, shows enhanced activity of some microsomal enzymes but not aryl hydrocarbon hydroxylase (AHH). However, it does have a rapidly active component which results in marked alteration of microsomal metabolism of benzo(a)pyrene. Another, for which a prototypical inhibitor is beta-naphthoflavone is characterized by induction of increased AHH activity. The third general mechanism of carcinogen inhibition entails the direct scavenging of reactive carcinogenic species by the inhibitor. Evidence supporting the psosibility that inhibitors play a role in the response of humans to carcinogens consists of three types. The first is the chemical diversity of the inhibitors and their actual occurrence in the environment. The second is the resposiveness of the detoxification systems, particularly those in the tissues of the major portals of entry, to the naturally-occurring or synthetic inhibitors. The third is a group of epidemiological studies which suggest that individuals consuming relatively large quantities of vegetables, a major source of naturally-occurring inhibitors, are at lower risk from gastrointestinal cancers.