The overall objective of this research project is to study chemopreventive agents that are designed to reach the large bowel and prevent colon cancer. A total of eight compounds that are derivatives of known inhibitors of chemical carcinogenesis will be synthesized. The ability of these proinhibitors to reach the colon and the rate of release of the active inhibitors will be determined. The concentration of the inhibitors in the colon contents and tissues will be analyzed. The induction of detoxifying enzymes that are associated with the inhibition of carcinogenesis as a result of the administration of proinhibitors will be determined in the liver, colon, and other tissues of laboratory animals. The mortality rate due to colorectal cancer in the United States is second only to lung cancer. This study uses the proinhibitors concept to design agents that are aimed to prevent cancer of the colon.
