RAPID SCREENING OF INHIBITORS OF COLON CARCINOGENESIS

THE MORTALITY RATE DUE TO COLORECTAL CANCER IS SECOND ONLY TO LUNG CANCER. ONE OF THE STRATEGIES TO REDUCE HUMAN CANCER IS BY CHEMOPREVENTION. WHILE THERE ARE A NUMBER OF CHEMICAL COMPOUNDS THAT SHOW GREAT PROMISE AS POTENTIAL CHEMOPREVENTIVE AGENTS, MORE SPECIFIC INHIBITORS OF COLON CARCINOGENESIS REMAINED TO BE DISCOVERED AND TESTED. WE WILL DEVELOP A RAPID IN VIVO SCREENING ASSAY THAT WILL BE USEFUL TO TEST A LARGE NUMBER OF CHEMICALS AS POTENTIAL INHIBITORS OF COLON CANCER. IN THIS PHASE I PROJECT, THE OPTIMUM CONDITION FOR THE ASSAY WILL BE DETERMINED USING STRAINS OF ANIMALS THAT ARE KNOWN TO PRODUCE COLON TUMORS. EARLY PRENEOPLASTIC LESIONS WILL BE INDUCED IN THE COLON MUCOSA BY COLON CARCINOGENS. THE INHIBITION OF THESE EARLY LESIONS BY INHIBITORS OF CARCINOGENESIS WILL BE DETERMINED WITHIN THREE WEEKS. THE TOTAL EXPERIMENTAL PERIOD FOR THIS ASSAY WILL BE LESS THAN FOUR WEEKS. BECAUSE OF THE SHORT DURATION REQUIRED FOR THIS ASSAY, LARGE NUMBERS OF COMPOUNDS MAY BE SCREENED WITH MUCH LESS EXPENSE THAN IN VIVO ANIMAL TUMOR MODELS. SINCE THE LESIONS PRODUCED ARE PRENEOPLASTIC IN NATURE THAT WILL EVENTUALLY ADVANCE TO CANCEROUS STATE, THIS TECHNIQUE MAY ALSO BE APPLICABLE AS A SCREENING ASSAY FOR COLON CARCINOGENS.