Clonal variation in albumin messenger RNA activity in hepatoma cells.

The clonal variation in rate of albumin synthesis in hepatoma cells is described as a tool for the study of epigenetic control of differentiation. Previous studies have demonstrated that, from a population of hepatome cells, variant subclones can be readily isolated that produce albumin at different rates. Each clonal variant had a characteristic rate of albumin production, and the clones clustered around discrete values that formed a geometric progression. The present experiments, using a cell-free protein-synthesizing system from wheat germ; show that albumin messenger RNA activity is directly proportional to the rate of albumin synthesis in three different hepatoma clones, thus suggesting a pretranslational control of albumin production. Possible hypotheses to explain the geometric pattern of clonal variation are discussed with respect to the organization and control of the transcriptional unit.