TK/ AND CHO HGPRT AND TK/ SUSPENSION ASSAYS THE MAJOR OBJECTIVE OF THIS STUDY IS TO IMPROVE THE ABILITY OF THE L5178Y TK/ ASSAY TO ESTIMATE THE MUTAGENIC POTENTIAL OF TEST COMPOUNDS.

TK/ AND CHO HGPRT AND TK/ SUSPENSION ASSAYS THE MAJOR OBJECTIVE OF THIS STUDY IS TO IMPROVE THE ABILITY OF THE L5178Y TK/ ASSAY TO ESTIMATE THE MUTAGENIC POTENTIAL OF TEST COMPOUNDS. SPECIFICALLY, MUTATION AT THE TK LOCUS OF L5178Y CELLS WILL BE COMPARED TO MUTATION AT THE HGPRT AND TK LOCI OF CHO CELLS TO DETERMINE IF THE TK/ TO TK/ MUTATION IN L5178Y CELLS IS REPRESENTATIVE OF MAMMALIAN GENE MUTATIONS. IN ADDITION, DISCREPANCIES BETWEEN EXISTING L5178Y AND RODENT CHRONIC STUDY RESULTS WILL BE EVALUATED AND AN ATTEMPT WILL BE MADE TO IMPROVE THE CORRELATION. AT THE END OF PHASE I: 1. SEVERAL POSITIVE AND NEGATIVE COMPOUNDS WILL HAVE BEEN SIMULTANEOUSLY TESTED IN THE L5178Y AND CHO SUSPENSION ASSAY, 2. A CHO TK/ HETEROZYGOTE WILL HAVE BEEN ISOLATED AND EVALUATED FOR NORMAL KARYOTYPE, LOW SPONTANEOUS 3. DISCREPANT RESULTS BETWEEN L5178Y ASSAY AND CHRONIC PHASE II STUDIES WILL CONSIST OF: 1. 2. SIMULTANEOUSLY TESTING COMPOUNDS IN THE L5178Y TK/ ASSAY AND CHO HGPRT AND TK/ ASSAYS, AND3. PERFORMING ADDITIONAL L5178Y ASSAYS ON TEST COMPOUNDS THAT GAVE DISCREPANT RESULTS BETWEEN THE L5178Y AND CHRONIC RODENT STUDIES. THIS PROJECT WILL BE INVALUABLE IN RE-ESTABLISHING THE L5178Y ASSAY AS CREDIBLE AND INDICATIVE OF GENE MUTATIONS. IN ADDITION, THE DEVELOPMENT OF A SECOND CELL LINE (CHO TK/) HAVING A SIMILAR ENDPOINT AND SHORT EXPRESSION PERIOD WILL BE A USEFUL TOOL FOR EVALUATING CHEMICALS FOR MUTAGENIC POTENTIAL.