A carcinogenesis- and tumorigenesis-associated rat fetal protein: an immuno-histochemical and immuno-biochemical study utilizing a new monoclonal antibody, MOFP

Abstract

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.

Liver Injury Models for Induction of Hepatic Oval Cells in Rodents

“…DEN can be given per-oral or intra-peritoneally, and/or in combination with other agents [47, 76,118]. Mouse models use DEN alone (intra-peritoneal) [119] while rat and hamster models use DEN (either per-oral or intra-peritoneal) in combination with 2-AAF and/or PH [53, 120,121]. For rats, oral preparations are dosed at 1mg per 100g body weight [120] while the intra-peritoneal dose is 15-20mg per 100g body weight [122,123].…”

“…Mouse models use DEN alone (intra-peritoneal) [119] while rat and hamster models use DEN (either per-oral or intra-peritoneal) in combination with 2-AAF and/or PH [53, 120,121]. For rats, oral preparations are dosed at 1mg per 100g body weight [120] while the intra-peritoneal dose is 15-20mg per 100g body weight [122,123]. In the DEN/2-AAF/PH model, peak oval cell response is seen 7 and 14 days after PH [85,124].…”

Variability of Neoplastic Parameters in Colon Tumours, and Its Significance in Diagnostic Practice

“…In experimentally induced hepatocarcinoma in rats, great similarity was found in tissue distribution of oncofetal protein, a potential marker for carcinogenesis, and MAb 17-IA specific for 17-I A antigen, an established surface marker for adenocarcinomas of the gastrointestinal tract (Oredipe et al, 1989).…”

Evaluation of oncofetal protein-related mRNA transport activity as a potential early cancer marker in dogs with malignant neoplasms

“…Subsequent study of 31 patients hospitalized for nonmalignant disease failed to reveal 55 -kd proteinassociated activity.13 A tivity.13 A tivity.13 monoclonal antibody (MAB) directed against the OFP purified from plasma of hepatomabearing rats was made , and 6 hybridomas were cloned. 14,15 The bioassay was modified by use of the MAB (clones C and E) to remove the mRNA transport activity, creating a more specific assay . The MAB (clones C and E) was used in immunohistochemical studies , western blot analysis , and a competitiveinhibition ELISA of rat tumors .…”