Phase II research will be directed toward further developing, defining, and evaluating a new host-mediated assay in which L5178Y mouse lymphoma cells heterozygous at the thymidine kinase locus, in diffusion chambers in mice are 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 a large number of chemicals in the mouse lymphoma host- mediated assay (MLHMA) will be compared with the results of testing the same chemicals inn 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 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.
