L5178Y MOUSE LYMPHOMA TK LOCUS HOST-MEDIATED ASSAY

PHASE I RESEARCH WILL BE DIRECTED TOWARD DEVELOPING A NEW HOST-MEDIATED ASSAY IN WHICH L5178Y MOUSE LYMPHOMA CELLS, HETEROZYGOUS AT THE THYMIDINE KINASE LOCUS AND IN DIFFUSION CHAMBERS IN MICE, WILL BE EXPOSED TO THE IN VIVO METABOLIC ACTIVATION AND DETOXIFICATION OF CHEMICALS. INDUCTION OF MUTAGENESIS WILL BE MEASURED IN VITRO. THE RESULTS OF TESTING SELECTED CHEMICALS IN THE MOUSE LYMPHOMA HOST-MEDIATED ASSAY (MLHMA) WILL BE COMPARED WITH THE RESULTS OF TESTING THE SAME CHEMICALS IN THE IN VITRO MOUSE LYMPHOMA CELL MUTAGENESIS ASSAY (MLA). IT IS ANTICIPATED THAT THE MLHMA WILL YIELD GREATER CONCORDANCE OF RESULTS WITH IN VIVO CARCINOGENESIS BIOASSAYSTHAN DOES THE MLA, AND THAT THE MLHMA WILL FILL A CURRENT URGENT NEED FOR AN EFFICIENT AND ECONOMICAL GENETIC TOXICOLOGY ASSAY TO MEASURE MUTAGENESIS IN MAMMALIAN CELLS FOLLOWING IN VIVO EXPOSURES TO CHEMICALS THAT MAY BE POTENTIALLY HAZARDOUS TO HUMANS. IF PHASE I RESEARCH IS SUCCESSFUL, LONGTERM PHASE II RESEARCH WILL BE PROPOSED TO DEVELOP MULTIPLE-ENDPOINT IN VIVO ASSAYS THAT INCORPORATE THE MLHMA AND TO EVALUATE A LARGER NUMBER OF CHEMICALS FROM DIVERSE CLASSES.