PHENOTYPE AND DIFFERENTIATION PATTERNS OF THE OVAL CELL-LINES OC CDE-6 AND OC/CDE-22 DERIVED FROM THE LIVERS OF CARCINOGEN-TREATED RATS/

An electron microscopic, immunocytochemical, and enzyme cytochemical a nalysis of the previously established oval cell lines OC/CDE 6 and OC/ CDE 22 was performed to characterize the phenotype and differentiation patterns of long-term cultures of oval cells, It was found that a-fet oprotein, albumin, and cytokeratin 19 are present in all cultured cell s, This indicates that oval cells constitute a population of immature cells expressing features of the antigenic phenotype of both the hepat ocyte and bile ductular cell lineages, An electron microscopic examina tion revealed a gradual alteration in the ultrastructure of oval cells toward hepatocyte-like cells. The majority of the oval cells were pos itive for glucose-6-phosphatase activity, A particularly striking obse rvation was that oval cells were heterogeneous in terms of peroxisome content, Only about 50% of the oval cells had peroxisomes in the cytop lasm, these cells probably being part of the hepatocyte lineage, The o ther cultured cells did not reveal catalase activity and probably repr esented cells committed to the bile ductular cell lineage, An addition of clofibrate to the culture medium resulted in a marked peroxisome p roliferation in all oval cells, indicating that oval cells might be ab le to change their differentiation pathway depending on environmental influence toward the hepatocyte lineage, It is most intriguing that in oval cells with abundant cytoplasm peroxisome proliferation was accom panied by proliferation of the smooth endoplasmic reticulum (this is a morphological marker of mature hepatocytes), Taken together, our find ings suggest that within the oval cell lines OC/CDE 6 and OC/CDE 22 ce lls undergoing a morphological and functional differentiation along th e hepatocyte and bile ductular cell lineages are present.