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, in diffusion chambers in mice, will be exposed to the in vivo metabolic activation and detoxification of chemicals, and the 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 lymophoma cell mutagenesis assay (MLA). It is anticipated that the MLHMA will yield greater concordance of results with in vivo carcinogenesis bioassays than 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, long-term Phass II research will be proposed to develop multiple endpoint in vivo assays which incorporate at the MLHMA and to evaluate a large number of chemicals, from diverse classes.
