A carcinogenesis- and tumorigenesis-associated rat fetal protein: an immuno-histochemical and immuno-biochemical study utilizing a new monoclonal antibody, MOFP.
An oncofetal protein (OFP), which is a potential marker for carcinogenesis and tumorigenesis, was evaluated with monoclonal antibodies shown to be specific for the antigen. Treatment of partially hepatectomized rats with a single non-necrogenic dose of diethylnitrosamine induced OFP in the liver. Its concentration, as measured by a dual immuno/bioassay, increased steadily over a 5-week period of observation before reaching a constant level. Immunohistochemical localization of OFP in liver sections from rats treated with N-nitroso-N-diethyl-nitrosamine showed that the factor was primarily localized to the cell cytoplasm in cells of most of the altered hepatic foci although some of this shedding antigen was also extracellular. Monoclonal antibody 17-1A specific for 17-1A antigen, an established surface marker for adenocarcinomas of the gastrointestinal tract, showed a similar distribution in liver from the carcinogen-treated rats, but localized to the cell membrane and cytoplasm. Scattered cells surrounding the altered hepatic foci were also positive for both monoclonal antibodies. Immunolocalization studies showed fetal rat liver and hepatoma were positive for OFP but adult normal or regenerating liver was negative. It was not detected in cells which morphologically could be classified as oval cells. As assessed by immuno/bioassay, the OFP released to the peripheral blood (plasma) of hepato-carcinogen-treated rats increased for 3 weeks, before undergoing a transitory decrease. Circulating antibodies specific for the factor were detected in the blood around 3-5 weeks post-treatment. Development of Western blots of the OFP with antiphosphotyrosine IgG indicates that the marker protein contains phosphotyrosine.
Oredipe
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Department of Pathology, College of Medicine, Ohio State University, Columbus 43210.
Schumm
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Mercurio
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Larroya
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Barth
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Webb
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D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000302:isolation & purification; D001681:Biological Assay; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D003600:Cytosol / Q000032:analysis; D004052:Diethylnitrosamine / Q000633:toxicity; D015151:Immunoblotting; D007074:Immunoglobulin G; D007700:Kinetics; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; C031192:oncofetal antigens; D004052:Diethylnitrosamine