The purpose of this project is to study the biolchemical role of polypeptides in neoplastic cellular development and proliferation. The aim of this work is to identify and characterize polypeptides that are involved in oncogenesis and to relate the differences in these species as possessed by normal or transformed cell phenotypes. These polypeptides can have activity as growth inhibitors (chalones) or promoters or as regulators of the cell cycle. The primary emphasis of effort will initially be concerned with investigations on the liver cell system. Polypeptide products from normal cells and cells obtained from chemically induced or spontaneous hepatomas will be tested and compared. Putative active materials will be identified by computer assisted two-dimensional gel electrophoresis and by in vitro tissue culture bioassay techniques. After promising candidates have been identified, they will be isolated and purified by techniques such as high pressure liquid chromatography, in amounts sufficient to do further biochemical characterizations. Amino acid sequence analysis will also be carried out on these materials to relate their various activities to their primary molecular structures. In ongoing studies with several hydrophobic transforming proteins obtained from virally infected cells, preliminary data has indicated that fatty acid moieties are covalently bound to these species, possibly allowing these proteins to associate with the cell membrane and cause conversion to the transformed phenotype. Studies on the effect of differentiation of HL60 cells on the incorporation of one of these fatty acids, myristic acid, have also been initiated.