Nature of the tumor-associated determinant(s) of carcinoembryonic antigen.
The carbohydrate moiety of carcinoembryonic antigen could be sequentially degraded by repeated cycles of periodate oxidation, reduction, and mild acid hydrolysis (Smith degradation). After three complete degradations, all fucose and sialic acid, 80% of the galactose, 65% of the mannose, and about 40% of the N-acetylglucosamine were eliminated without impairing the ability of degraded carcinoembryonic antigen to react with specific antisera against the antigen. Inhibition studies in a carcinoembryonic antigen/rabbit anti-carcinoembryonic antigen precipitating system with oligosaccharides covering previously known internal structures of glycoproteins and presumably corresponding to the internal carbohydrate region of the antigen, demonstrated that none of the compounds tested was inhibitory. Nor could any inhibitory effect on the binding of carcinoembryonic antigen to antibody against the antigen in a radioimmunoassay system be domonstrated for the carbohydrate moiety prepared by hydrazinolysis or the glyco peptide fraction isolated after papain degradation of the antigen. However, if carcinoembryonic antigen is completely reduced and alkylated, with three intrachain disulfide bonds cleaved per 10-5 g, the immunological activity is reduced to 3-5% of untreated antigen. Furthermore, treatment of the antigen with 0.5 NaOH at 20 degrees for 2 hr completely abolished its ability to react with antiserum, whereas its ability to precipitate with a series of lectins was unchanged. No release of low-molecular-weight carbohydrate orchange in sugar composition of alkali-treated antigen was observed. Our tentative conclusion is that the carbohydrate moiety of carcinoembryonic antigen does not contain the tumor-associated determinant(s).
D000116:Acetylgalactosamine / Q000032:analysis; D000117:Acetylglucosamine / Q000032:analysis; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000302:isolation & purification; D006528:Carcinoma, Hepatocellular / Q000032:analysis; D003110:Colonic Neoplasms / Q000032:analysis; D000939:Epitopes; D005455:Fluorescent Antibody Technique; D005643:Fucose / Q000032:analysis; D005690:Galactose / Q000032:analysis; D006801:Humans; D037102:Lectins; D008099:Liver / Q000032:analysis; D008113:Liver Neoplasms; D008358:Mannose / Q000032:analysis; D009362:Neoplasm Metastasis; D009844:Oligosaccharides / Q000032:analysis; D010206:Papain; D011233:Precipitin Tests; D011817:Rabbits / Q000276:immunology; D011863:Radioimmunoassay; D012794:Sialic Acids / Q000032:analysis
D002272:Carcinoembryonic Antigen; D000939:Epitopes; D037102:Lectins; D009844:Oligosaccharides; D012794:Sialic Acids; D005643:Fucose; D010206:Papain; D000116:Acetylgalactosamine; D008358:Mannose; D000117:Acetylglucosamine; D005690:Galactose