Discontinuous Variability, in the Form of a Geometric Progression, of Albumin Production in Hepatoma and Hybrid Cells

A clonal rat hepatoma cell line (Fu5) produces rat serum albumin at a constant rate over at least 3 months of continuous cultivation. Ten hybrid cell clones derived from the fusion of Fu5 cells and mouse fibroblasts, as well as 14 hepatoma subclones of Fu5 cells, all produce albumin but at different rates, ranging from about 0.09 to 36.7 μg/mg of protein per 72 hr. Despite this variability in albumin production, the distribution of clones is not random but discontinuous, with both hepatoma and hybrid clones clustering around discrete values that can be fitted to the geometric progression:a ,a (√2)1 ,a (√2)2 a (√2)n . The values of the majority of clones fall into alternate members of this geometric progression, which differ by a factor of 2. Hepatoma subclones with indistinguishable karyotypes differ in level of albumin production by as much as 4-fold. In contrast to hepatoma clones, albumin production in hybrid clones decreases with increasing cell generations. A survey of 28 enzymes of different hepatomas reveals a large variability in enzyme levels which, for most enzymes, can be arranged into classes that form a geometric progression. The apparent widespread nature of this discontinuous phenotypic variability suggests that it may reflect a basic mechanism of control of gene expression in animal cells.