CHEMOPREVENTIVE AGENTS

THE OVERALL GOAL OF THIS STUDY IS THE DEVELOPMENT OF TWO IN VITRO TRANSFORMATION ASSAYS FOR THE EVALUATION OF CHEMO- PREVENTIVE AGENTS. THE TWO SYSTEMS UTILIZE PRIMARY SYRIAN HAMSTER EMBRYO CELLS AND RETROVIRAL-INFECTED FISCHER RAT EMBRYO CELLS (A CONTINUOUS CELL CULTURE). BOTH CELL TYPES ARE ROUTINELY TRANSFORMED BY CARCINOGENIC CHEMICALS WITH THEANCHORAGE-INDEPENDENT GROWTH ENDPOINT ASSOCIATED WITH TUMORIGENICITY. MODEL CHEMOPREVENTIVE AGENTS (INHIBITORS OFPROSTAGLANDIN SYNTHESIS AND PROTEASE INHIBITORS) WILL BE USED TO INHIBIT TRANSFORMATION BY CHEMICAL CARCINOGENS. CONDITIONS FOR MAXIMUM EFFECTIVENESS OF THE SELECTED CHEMO- PREVENTIVE AGENTS WILL BE ESTABLISHED DURING THIS PHASE I PROJECT. DURING PHASE II, THE USE OF FLUORESCENT ANTIBODIESTO ONCOGENE PRODUCTS WILL BE INVESTIGATED AS A MEANS OF DETECTING THE EMERGENCE OF MALIGNANT CELLS EARLIER THAN IS SEEN BY COLONY FORMATION IN SOFT AGAROSE. THIS WILL ALLOW MORE EFFECTIVE MEANS OF EVALUATING CHEMOPREVENTIVE AGENTS.