Intraclonal variation in proliferative potential of human diploid fibroblasts: stochastic mechanism for cellular aging.

At several points during the growth of a clone of human embryonic lung fibroblasts in vitro, 100 to 200 cells were removed at random and the proliferative potential of each cell was determined. At each sample point, a wide variation in remaining population doubling ability was observed among the individual cells and the distributions of doubling potentials were distinctly bimodal. Furthermore, the two cells arising from a single mitosis differed in their ability to proliferate by as many as eight population doublings (256-fold in the number of cells produced). The results suggest that a stochastic process is responsible for determining the limited proliferative potential of human embryonic lung fibroblasts.