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Cancer Chemoprevention Agent Development Strategies for Genistein¹

Vernon E. Steele^2,*, Michael A. Pereira, Caroline C. Sigman and Gary J. Kelloff^*

^* Chemoprevention Branch, Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD 20892 CCS Associates, 1965 Landings Drive, Mountain View, CA 94043 Department of Pathology, Medical College of Ohio, 3000 Arlington Avenue, Toledo, Ohio 43614

Cancer chemoprevention refers to the reduction of cancer incidence by administration of agents or drugs that inhibit, reverse or retard the cancer process. Genistein has demonstrated a wide variety of biological activities that make it a good candidate for a chemopreventive agent. Many agents, such as genistein, are currently being tested with the goal of developing safe and effective chemopreventive drugs for human use. Genistein was investigated as a potential chemopreventive agent in an azoxymethane-induced colon carcinogenesis model. Genistein was tested for its ability to inhibit aberrant colon crypts in the colon of F344 rats that had been treated with azoxymethane. Genistein was administered in the diet from 1 wk before the carcinogen to 4 wk after the first carcinogen dose for a total of 5 wk. At both doses, 75 and 150 mg/kg, the mean number of foci per colon was significantly reduced. Further development of this agent includes demonstration of the preventive efficacy in an in vivo tumorigenesis model, followed by preclinical pharmacology and toxicology testing. Phase 1, 2 and 3 clinical chemoprevention trials would be then performed to determine pharmacokinetics, safe doses, and effectiveness for New Drug Approval.

KEY WORDS: • chemoprevention • genistein • drug development • carcinogenesis • cancer prevention

¹ Presented at the First International Symposium on the Role of Soy in Preventing and Treating Chronic Disease, held in Mesa, AZ, February 20–23, 1994. The symposium was sponsored by Protein Technologies International, the soybean growers from Nebraska, Indiana and Iowa and the United Soybean Board. Guest editors for this symposium were Mark Messina, 1543 Lincoln Street, Port Townsend, WA 98368, and John W. Erdman, Jr., Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801-3852.

² To whom correspondence should be addressed: Chemoprevention, EPN-201, NCI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 [(301)496-8563, FAX: (301)402-0553].

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