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.