Oval cell lines OC/CDE 6 and OC/CDE 22 give rise to cholangio-cellular and undifferentiated carcinomas after transformation.

BACKGROUND

There is compelling evidence for a parenchymal origin of the predominant cell lineage leading from preneoplastic clear and acidophilic glycogen storage foci through mixed and basophilic cell populations to hepatocellular carcinomas in the rat. However, a controversial question remains to be answered: Do the basophilic cell foci invariably originate from parenchymal cells or do oval cells also have the potential to give rise to this type of focus and progress to hepatocellular neoplasms? Oval cells are nonparenchymal epithelial cells with scant cytoplasm and ovoid nuclei that first appear in the periportal areas of the liver lobules and thereafter invade the whole parenchyma when animals are exposed to high doses of a wide range of chemical carcinogens.

EXPERIMENTAL DESIGN

Two oval cell lines, OC/CDE 6 and OC/CDE 22, which had been established from rats fed a choline-deficient/DL-ethionine-supplemented diet for 6 or 22 weeks, were transformed either by leaving the cells in confluence for a long time period (OC/CDE 6) or by treating the cells with the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. The transformed cells were injected subcutaneously in newborn rats and the tumors developing in these animals were analyzed histopathologically, ultrastructurally, and immunohistochemically.

RESULTS

The two transformed oval cell lines gave rise to carcinomas, in which cholangiocellular, adenoid and solid tumor formations were observed. Subpopulations of these tumors expressed cytokeratins 7, 8, 18, and 19, but were albumin- and alpha-fetoprotein-negative. Areas within the carcinomas derived from transformed OC/CDE 22 cells representing undifferentiated liver tumor formations were also identified. Cells within these areas had lower nucleus/cytoplasm ratios than cells in the solid growing tumor formations, stained positive for cytokeratins 8 and 18 and were cytokeratin 7- and 19-, albumin- and alpha-fetoprotein-negative. Ultrastructurally, these cells did not resemble those of differentiated hepatocellular carcinomas.

CONCLUSIONS

It has been shown that oval cells are precursor cells of carcinomas containing cholangiocellular, adenoid and solid formations which may be largely undifferentiated. However, the transformed OC/CDE 6 or OC/CDE 22 cells do not serve as precursor cells of differentiated hepatocellular carcinomas.