Quantitative phenotypic variation in single normal and malignant cells from liver and breast occurs along a geometric series.
Single-cell variability in albumin content of normal rat hepatocytes and hepatoma cells and in a specific breast surface antigen content in normal and malignant human mammary epithelial cells was studied by a quantitative immunoperoxidase method. The range of variability was nearly 10-fold for both normal and malignant cells. This wide range of single cell heterogeneity was generated very rapidly in clonal colonies of less than 30 hepatoma cells. By a grid test for periodicity that we devised, and also by Fourier transform analysis, the distribution of albumin content in single hepatocytes and hepatoma cells, and of a breast surface antigen content in normal and malignant breast cells, was shown to be discontinuous, where the cells distributed with a periodicity that fit a geometric series, of which consecutive values differed by a factor of square root 2. The fit to this geometric series was best for normal cells. Significant quantal shifts occurred at a high rate (greater than 10(-2) per cell per generation) and to higher and lower levels with equal probability. These results demonstrate that geometric phenotypic variability is a normal phenomenon and should be taken into account when studying gene regulation and population dynamics.
D000818:Animals; D001940:Breast / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008099:Liver / Q000502:physiology*; D008114:Liver Neoplasms, Experimental / Q000235:genetics*; D010641:Phenotype; D051381:Rats; D012709:Serum Albumin / Q000235:genetics*
D012709:Serum Albumin