DIFFERENTIATED CELLS AS TARGETS FOR CARCINOGEN-SCREENING

THE OVERALL OBJECTIVE IS TO DEVELOP A NEW SYRIAN HAMSTER EMBRYO (SHE) MORPHOLOGICAL TRANSFORMATION ASSAY (MTA) EMPLOYING SPECIFIC CELL TYPES AS TARGETS AND USING DEFINED, SERUM-FREE CULTURE MEDIA. SPECIFIC AIMS FOR PHASE I STUDY INCLUDE: (1) ISOLATION AND CHARACTERIZATION OF SPECIFIC CELL TYPES (CHONDROCYTES, MYCOCYTES, FIBROBLASTS, ENDOTHELIAL CELLS) FROM SHE AS TARGETS FOR THE IN VITRO TRANSFORMATION ASSAY; (2) ADAPTATION OF EACH OF THE SELECTED TARGET CELL TYPES TO GROW IN APPROPRIATE SERUM-FREE GROWTH MEDIA; (3) DEVELOPMENT OF A PROTOTYPE SERUM-FREE MEDIUM THAT ENHANCES THE TRANSFORMED PHENOTYPE. TECHNICAL INNOVATION IN THIS PROJECT LIES IN THE SUBSTITUTION OF DEFINED FACTORS IN PLACE OF SERUM AND AVOIDANCE OF THE USE OF X-IRRADIATED "FEEDER" CELLS THAT MIGHT REPRESENT PREFERRED TARGETS FOR PARTICULAR CARCINOGENS WOULD CONSTITUTE AN IMPORTANT IMPROVEMENT OVER CURRENT MTAS. PROCEDURES AND REAGENTS DEVELOPED WILL BE USEFUL IN SCREENING ENVIRONMENTAL CHEMICALS FOR THEIR CARCINOGENIC POTENTIAL, HENCE COMMERCIALLY VALUABLE.