DEDIFFERENTIATED VARIANTS OF A RAT HEPATOMA - ANALYSIS BY CELL HYBRIDIZATION

Two independent dedifferentiated variants, H5 and FaoflC2, derived from the Reuber H35 hepatoma, produce trans-acting diffusible substance(s) that extinguish the expression of liver-specific proteins when hybridized with a well-differentiated cell line of the same origin (Fao and Fu5-5, respectively). H5 .times. Fao hybrids show total and stable extinction of 4 liver functions and clonal variability in the expression of 3 others. FaoflC2 .times. Fu5-5 hybrids are initially flat (like FaoflC2 cells), and die in glucose-free medium where survival requires expression of hepatic gluconeogenic enzymes, but then evolve to hepatoma-like and finally round morphology; these latter cells express all liver functions analyzed including the gluconeogenic enzymes. Two exceptional clones that remained flat long enough for complete analysis showed extinction of all hepatic functions not expressed by FaoflC2 cells. This transitory extinction may reflect the action and then loss of extinguishing factor(s) contributed by FaoflC2. When crossed with BW1-J mouse hepatoma cells, FaoflC2 causes stable extinction of mouse aldolase B. Production of extinguishing factor(s) apparently is the rule for dedifferentiated variants.