The purpose of this project is to characterize the enzyme pathways which support aerobic glycolysis in neoplastic cells and tumors. Studies in progress are the following: (1) Characterization of protein modifications in lactate dehydrogenase in relationship to the increased secretion of lactic acid in the chemically transformed neoplastic cell. Control rat liver epithelial cells in culture show a constant ratio of activity and LDH-r and -5 compared with corresponding chemically transformed cells up to passage 21, but LDH activity in the control cells increases as the passage number increases above 21 and the LDH-4 and -5 become equal in reactivity. As the passage number increases, LDH from control cells approaches but does not equal that of the neoplastic cells. Comparison of LDH isozyme from epithelial and fibroblastic lines show that each retains the characteristics of the parent cell even following neoplastic transformation. (2) Studies on changes in the ultrastructure of control and neoplastic cells related to cytoskeletal complexes of tubulin, cytokeratin, and actin are underway. (3) Analyses of spectrophotometric absorption components of mitochondria, and analysis of total heme content of control and chemically-transformed neoplastic cell lines are being performed. (4) The breakdown product of heme proteins is evaluated in relationship to reduced numbers of mitochondria and depleted structures in neoplastic cells.
