TRANSGENIC RATS - A SHORT-TERM MUTAGENICITY ASSAY

THIS RESEARCH OUTLINES THE DEVELOPMENT OF TRANSGENIC RAT MODEL FOR SHORT-TERM SCREENING OF SUSPECTED MUTAGENS. THE RECENT USE OF LAMBDA PHAGE SHUTTLE VECTORS IN TRANSGENIC MIC MAKES POSSIBLE THE RAPID IN VIVO SCREENING OF MUTATIONS. SUCH SYSTEMS WILL PERMIT QUANTITATIVE TISSUE SPECIFIC DETERMINATION OF MUTANT RATES, AND COUPLED WITH ADDITIONAL QUANTITATIVE MEASURES (E.G. DNA ADDUCT LEVELS) WILL ALLOW FOR DIRECT DETERMINATION OF THE CONTRIBUTION OF METABOLIC PROCESSES, CELL PROLIFERATION, DETOXIFICATION, DNA REPAIR, AND THE ROUTE OF DOSING ON MUTAGENESIS. THE LOGICAL EXTENSION OF THIS SYSTEM TO RATS WILL PERMIT DIRECT SPECIFIC COMPARISON AT THE MOLECULAR LEVEL FOR CHEMICAL SCREENING. CURRENTLY, HUMAN RISK ASSESSMENT IS PERFORMED THROUGH THE EXTRAPOLATION OF TUMORIGENICITY DATA OBTAINED FROM MULTIPLE SPECIES SHOULD IMPROVE INTERSPECIES EXTRAPOLATION TO HUMANS THROUGH AN INCREASED MECHANISTIC UNDERSTANDING OF HOW CHEMICALS DIFFERENTIALLY INDUCE MUTATIONS.