Selective isolation of stable and unstable dedifferentiated variants from a rat hepatoma cell line

This paper describes the selective isolation of dedifferentiated variants from a well-differentiated rat hepatoma cell line (Fao). The well-differentiated cells express the gluconeogenic enzymes, FDPase and PEPCK, and so can grow in a glucose-free medium. By using glucose-free medium in conjunction with the BudR-visible light suicide technique it was possible to isolate two different classes of dedifferentiated variants from a mutagenized population of Fao cells. The variants of the first class resemble those previously described in that they display (1) an altered cellular morphology, (2) a pleiotrophic loss of all (or most) of the hepatic functions routinely analyzed in this laboratory, and (3) an extremely low reversion frequency (less than or equal to 10-8). The variants of the second class are characterized by an unstable phenotype and uncoordinated expression of the hepatic functions. Unstable variants can give rise to stable dedifferentiated variants, suggesting that the unstable variants may actually represent an intermediate in a two-step dedifferentiation process.