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)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034635-04
Application #
3172400
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1983-04-01
Project End
1988-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
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Faris, R A; McEntire, K D; Thompson, N L et al. (1990) Identification and characterization of a rat hepatic oncofetal membrane glycoprotein. Cancer Res 50:4755-63
Moriyama, T; Guilhot, S; Klopchin, K et al. (1990) Immunobiology and pathogenesis of hepatocellular injury in hepatitis B virus transgenic mice. Science 248:361-4
Dunsford, H A; Karnasuta, C; Hunt, J M et al. (1989) Different lineages of chemically induced hepatocellular carcinoma in rats defined by monoclonal antibodies. Cancer Res 49:4894-900
Chisari, F V; Klopchin, K; Moriyama, T et al. (1989) Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell 59:1145-56
Scott, R J; Chakraborty, S; Sell, S et al. (1989) Change in the ploidy state of rat liver cells during chemical hepatocarcinogenesis and its relationship to the increased expression of alpha-fetoprotein. Cancer Res 49:6085-90
Sell, S; Hunt, J M; Knoll, B J et al. (1987) Cellular events during hepatocarcinogenesis in rats and the question of premalignancy. Adv Cancer Res 48:37-111
Dunsford, H A; Maset, R; Salman, J et al. (1985) Connection of ductlike structures induced by a chemical hepatocarcinogen to portal bile ducts in the rat liver detected by injection of bile ducts with a pigmented barium gelatin medium. Am J Pathol 118:218-24