CHEMOPREVENTION BY NATURALLY-OCCURRING AND SYNTHETIC AGENTS IN ORAL, LIVER, AND LARGE-BOWEL CARCINOGENESIS

A number of naturally occurring compounds and several related syntheti c agents were confirmed to exert chemopreventive properties against ca rcinogenesis in the digestive organs. Phenolic compounds, widely distr ibuted as plant constituents, possess chemopreventive activities in to ngue, liver, and large bowel of rodents. Of them, a simple phenolic pr otocatechuic acid seems to be a promising compound. Organosulfur compo unds contained in the cruciferous vegetables and known to activate det oxifying enzymes are regarded as a candidate group for cancer preventi ve agents. We proved a strong protective effect of S-methylmethanethio sulfonate, a constituent in these vegetables, on azoxymethane (AOM)-in duced large bower carcinogenesis. Some oxygenated carotenoids (xanthop hylls) are reported to have antitumor effects. Naturally occurring xan thophylls astaxanthin and canthaxanthin have considerable preventive a ctivities on 4-nitroquinoline-1-oxide (4-NQO)-induced tongue carcinoge nesis and AOM-induced large bowel carcinogenesis. A novel synthesized retinoidal butenolide, KYN-54, which suppresses large bowel as well as tongue carcinogenesis, could be a useful agent for prevention of dige stive organ cancers. Some trace elements are known to have anticarcino genic effects. Magnesium hydroxide, a protective agent in colorectal c arcinogenesis, inhibits c-myc expression and ornithine decarboxylase a ctivity in the mucosal epithelium of the intestine. Our results show t hat many agents with preventive effects in tongue, liver, and large bo wel control carcinogen-induced hyperproliferation of cells in these or gans. Carcinogens used to induce large bower cancers also induce apopt osis in the target sites. Telomerase activity is increased in the tiss ues of preneoplastic as well as neoplastic lesions in experimental mod els such as dimethylbenz[a]anthracene-induced oral carcinogenesis in h amsters. These could be useful biomarkers in studies for cancer chemop revention. (C) 1998 Wiley-Liss, Inc.dagger