THE OBJECTIVE OF THIS PROJECT IS TO ESTABLISH INNOVATIVE SCREENING SYSTEMS THAT IDENTIFY NEW CHEMOPREVENTIVE AGENTS, USING DIFFERENT IN VITRO MODELS OF ONCOGENESIS.

THE OBJECTIVE OF THIS PROJECT IS TO ESTABLISH INNOVATIVE SCREENING SYSTEMS THAT IDENTIFY NEW CHEMOPREVENTIVE AGENTS, USING DIFFERENT IN VITRO MODELS OF ONCOGENESIS. THREE POTENTIAL SYSTEMS, EACH REPRESENTING A DIFFERENT STAGE IN THE CARCINOGENIC PROCESS, WILL BE TESTED AGAINST SELECTED CHEMOPREVENTIVE AGENTS. PHASE I EFFORTS INVOLVE DETERMINATION OF THE INHIBITORY EFFECTS OF RETINOIDS ON: A.IMMORTALIZATION AND MALIGNANT TRANSFORMATION INDUCED BY CARCINOGENIC AGENTS (AFLATOXIN B1, ULTRAVIOLET RADIATION, ONCOGENES) IN VITRO IN NORMAL DIPLOID EPITHELIAL CELL CULTURES DERIVED FROM RAT LIVER. B.EXPRESSION OF THE MALIGNANT PHENOTYPE IN A TEMPERATURE-SENSITIVE MUTANT LINE DERIVED FROM A CHEMICALLY TRANSFORMED LIVER CELL LINE, AND IN THE WILD TYPE CELLS. C.INDUCTION OF MORPHOLOGICAL TRANSFORMATION IN FIBROBLASTIC CELL LINES (NIH 3T3 AND C3H 10T1/2 CLONE 8) BY TRANSFECTION DURING PHASE I, EXPERIMENTAL CONDITIONS AND VARIABLES WILL BE STANDARDIZED FOR EACH OF THE ABOVE MODEL SYSTEMS THE RESULTS OF WHICH ARE EXPECTED TO IDENTIFY THEIR FEASIBILITY AS POTENTIAL SCREENING SYSTEMS FOR CHEMOPREVENTIVE AGENTS. DURING PHASE II, THE APPROPRIATE SYSTEM(S) WILL BE FURTHER DEVELOPED USING DIVERGENT CHEMOPREVENTIVE AGENTS, PRIOR TO THE EVENTUAL COMMERCIALIZATION OF THIS IN VITRO BIOASSAY FOR NEW CHEMOPREVENTIVE AGENTS.