The goal of this project is to produce monoclonal antibodies to premalignant cell populations during chemical hepatocarcinogenesis in rats to determine whether or not expression of these phenotypes can be used to provide a clearer understanding of carcinogenic progression and the lineage of hepatocellular carcinoma. We have isolated oval cells from rats after brief exposure to n-2-acetylaminofluorene in a choline deficient diet, immunized mice, and raised monoclonal antibodies to oval cells and normal hepatocytes. Isolated preneoplastic cells from other carcinogenic regimens have been used to raise additional monoclonal antibodies to oval cells, nodular hepatocytes, and normal hepatocytes. These monoclonal antibodies (and additional ones to be developed) will be characterized and used to study the epitopes on preneoplastic cells that appear during experimental models of carcinogenesis. These studies will delineate lineages of progression of normal cells to cancer cells. In addition, these monoclonal antibodies have been used to isolate specific preneoplastic cell populations from carcinogen-treated livers by fluorescent cell sorting, and the potential malignancy of these populations will be tested by transplantation into syngeneic rats. (2)
