Two systems with potentially wide application will be developed for the rapid, sensitive, and quantitative detection of certain classes of mutagens and prospective carcinogens: (a) Genetic studies will be made of a Salmonella typhimurium "mutator" strain that we have isolated which is 10-fold more sensitive to a frameshift mutagen ((hycanthone) and is now equally responsive to lucanthone (miracil D), a closely related compound that fails to mutate a wide variety of strains including all of the Ames tester strains. The gene responsible for enhanced sensitivity and widened mutagen profile will be mapped. Using various histidine mutations of known response and various mutagens of known modes of action, the pattern of increased mutagenesis will be defined and the utility as a "tester strain" (with and without rfa and pKM101 additions) will be evaluated. Other strains will be sought that are highly responsive to particular base-substitution mutagens (e.g., methyl-N-nitrosoacetamide and aryl-monoalkyl triazene, whose genetic activities are unaffected by the presence of the uvrB gene product). Successive mutagenesis of a multiply auxotrophic strain carrying a series of base-substitution mutations will be used to procure mutagen-hypersusceptible strains. (b) Refined techniques will be developed for ready detection and scoring of foci of metaplasias in the gastrointestinal tracts of mice (e.g., gastric intestinal metaplasia). Plaque detection will utilize histochemical staining (e.g., alkaline phosphatase) and immunofluorescence (e.g., antibodies directed against epithelial cell suspensions and glycoproteins). Possible monoclonality of foci of metaplasia in heterozygous female mice will be examined by analyses of PGK (Phosphoglycerate kinase) isozyme content after microhomogenization and electrophoresis.