An ultrastructural study of rat hepatoma cells in culture, their variants and revertants.

We compared the ultrastructure of a well-differentiated rat hepatoma line (H4II) and its clonal progeny, including dedifferentiated variant cells, and revertants of the variants in which the spectrum of hepatocyte-specific functions is again expressed. The cells of the original differentiated lines and the revertants were very similar to one another. In addition, they exhibited some of the characteristics of fetal and neonatal hepatocytes. Variant cells which fail to express hepatocyte functions showed a wide range of morphological alterations accompanied by generalized disorganization. It is concluded that the loss of hepatocyte differentiation in the variants is not associated with a uniform morphological type, and that a wide range of ultrastructural phenotypes can be generated in the progeny of a single neoplastic but well-differentiated hepatocyte. Also, the expression of hepatocyte functions only occurs within a limited and organized morphological framework that includes features of young hepatocytes.