The objectives are to synthesize stable derivatives of the human fecal mutagen, fecapentaene, and study their effects as colon carcinogens. In this Phase I study, four derivatives of fecapentaene-12 will be synthesized. The partition coefficients of these derivatives which measure the lipophilicity and absorption pattern of compounds across cell membranes, will be determined. Tie ability of the fecapentaene derivatives to reach the colon and the rate of fecapentaene release will be determined. The concentration of the mutagen in the colon contents and tissues will be analyzed after administration of the derivatives. Since the discovery of fecapentaenes as a major component of human fecal mutagens, there have been intensive research to establish their validity as human carcinogens. The effort towards this goal has been complicated by the instability of these compounds. This research will attempt to solve this problem by designing derivatives of fecapentaenes that will survive the environment of the upper gastrointestinal tract and allow the parent compounds to be released in the colon. The availability of these stabile fecapentaene derivatives to the scientific community will help the overall effort to understand the relationships of fecapentaenes and colon cancer.Awardee's statement of the potential commercial applications of the research: Stable derivatives of the fecal mutagens, fecapentanes, will provide a valuable set of model compounds for the study of human colon cancer.National Cancer Institute (NCI)
