Monoclonal antibodies reacting with normal rat liver cells as probes in hepatocarcinogenesis.
A series of four monoclonal antibodies was raised against suspensions of normal adult WAB/Not rat hepatocytes. An immunoperoxidase-staining technique was used to examine the distribution of determinants detected by these antibodies on frozen sections of fetal, neonatal, adult, and regenerating liver and on a range of 4-dimethylaminoazobenzene-induced liver lesions, including a panel of 32 primary liver carcinomas. Three of the antibodies were directed against hepatocytes, while a fourth antibody stained stromal elements within the liver. The determinants detected by the anti-hepatocyte monoclonal antibodies arose in a specific sequence during normal liver development and, when assessed in conjunction, characterized several phenotypes associated with stages in normal hepatocyte differentiation. These same antibody-defined phenotypes were expressed by the primary liver carcinomas, and the distribution of phenotypes among the tumors revealed a heterogeneity which was not evident from a conventional morphological classification. Primary liver tumors expressed a total of four antibody-defined phenotypes, whereas gamma-glutamyl transpeptidase-positive foci of hepatocytes and neoplastic nodules expressed, respectively, only one or 2 antibody-defined phenotypes. We suggest that monoclonal antibodies directed against normal liver cell components may provide a means to establish lineage relationships between cell populations involved in hepatocarcinogenesis.
D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D000939:Epitopes / Q000032:analysis; D007124:Immunoenzyme Techniques; D008099:Liver / Q000276:immunology*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000276:immunology*; D008115:Liver Regeneration; D051381:Rats; D011919:Rats, Inbred Strains; D004124:p-Dimethylaminoazobenzene
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000939:Epitopes; D004124:p-Dimethylaminoazobenzene