Chemically induced hepatocarcinogenesis is accompanied by the emergence of new cell populations exhibiting defective control of cellular proliferation and positional order, a phenotypic expression that presumably involves alterations of plasma membrane glycoproteins. The objective of this research is to identify the appearance of new or inappropriate cell-surface glycoproteins, as well as he deletion or structural modification of normally expressed glycoproteins. Cell populations being studied include hepatocytes, primary and transplantable hepatocellular carcinomas, and focal or nodular proliferative lesions associated with chemically (2-acetylaminofluorene, diethylnitrosamine, or ethionine) induced hepatocarcinogenesis in the ACI rat. Cells are radioactively labeled using methods specific for cell-surface proteins and glycoconjugates. The surface-labeled components are solubilized in detergents and resolved by lectin affinity chromatography and polyacrylamide gel electrophoresis. Glycoproteins exhibiting properties unique to normal or malignant cells are identified and xenoantisera (mono- and polyclonal) reactive with these altered components are prepared. These antisera, as well as antisera against purified plasma membrane glycoproteins, known to undergo alteration during hepatocarcinogesis, e.g., Lambda-glutamyl transpeptidase, will be used to probe plasma membrane alterations in other cell populations associated with hepatocarcinogenesis. These immunological reagents are being used to delineate alterations in the composition, structure, and topography of the plasma membrane glycoproteins of cell populations associated with hepatocarcinogenesis, thereby contributing to our understanding of the role of these cell-surface components as determinants of the biological properties of the malignant cell and its progenitors.
