Metabolic conversion of chemical carcinogens into the active, or proximate form, has for at least the past three years been a major aspect of this project. Emphasis continues to be on the enzymes converting polycyclic hydrocarbons, with particular reference to genetic variation in man. Efforts during the past year have been directed toward improving the human assay methods. Further study of cancer patients supports evidence that lung cancer patients have a higher inducibility of the major enzyme (AHH). Preliminary evidence also indicates that patients with squamous cell carcinoma of the nasopharynx are similarly elevated. Additionally, we are employing strains of mutant bacteria to detect actively mutagenic metabolites of carcinogens, particularly the metabolites of acetylaminofluorene (AAF) and the enzymes which carry out its activation. Use of electrophoretically variant enzymes as genetic markers continues to play a role in some of the projects supported by this grant. The methodology has been modified to study newly synthesized proteins in developing embryos by autoradiographic techniques. The enzyme (isozyme) markers are used in ongoing studies of genetic divergence among species, in analysis of altered forms of enzymes in suppressor strains of bacteria, and in detection of experimentally induced mutations in cultured mammalian cells. BIBLIOGRAPHIC REFERENCES: Shaw, Charles R. and Michael J. Siciliano. Separation and Visualization of Enzymes on Gels. In, Chromatographic and Electrophoretic Techniques, Vol. 2, Zone Electrophoresis, ed. Ivor Smith, Wm. Heinemann Medical Books Ltd., London, 1976. Shaw, Charles R. Chemical Carcinogenesis: Who is susceptible? Harper's, June, 1976.