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Strategy of research for cancer--chemoprevention.

It has been reported that environmental chemicals are important factors in terms of both development and prevention of human cancer. For the latter, detection of early stages is an essential first step followed by clinical trials for surveying populations at risk. Thus a great deal of attention has been focused on these areas. However, investigations of possibilities for active prevention of cancer development itself form another major project. Chemoprevention of carcinogenesis, which means prevention of carcinogenesis by exogenous chemical compounds, has been investigated extensively in a variety of organs in animal models. Usually attention is concentrated on only one organ. However, antioxidants, such as BHA, exert very different effects on different organs, suggesting the necessity of whole body approaches to the question of chemoprevention. Furthermore, the mechanisms of chemoprevention, including the step of carcinogenesis, i.e., initiation, promotion, progression or whole carcinogenesis steps, in which exogenous compounds exert their protective effects, should be considered. A medium-term bioassay system and a multi-organ carcinogenesis system, which can be used for investigation of potential for cancer chemoprevention, have been developed in our laboratory. Dose dependent inhibitory effects were established for both BHA and alpha-tocopherol in the medium-term bioassay system, and inhibition of small intestinal carcinogenesis by catechins in green tea has also been investigated in our multi-organ carcinogenesis protocol. It is extremely important for prevention of human cancer that we find new candidates for chemopreventive agents using animal studies. This paper reviews published reports on chemoprevention, taking into account effective stages, and proposes suitable experimental animal models for future investigations in this increasingly important area.