A model of clonal attenuation.
Two formal models of clonal attenuation [Kirkwood, T. B. L. & Holliday, R. (1975) J. Theor. Biol. 53, 481-496; Shall, S. & Stein, W. D. (1979) J. Theor. Biol. 76, 219-231] are considered in the light of recent data on the changing distribution of replicative potential among individual cultured fibroblasts on subcloning. The experimental data [Smith, J. R., Pereira-Smith, O. & Good, P. I. (1977) Mech. Ageing Dev. 6, 283-286] are shown to contradict both models. A new model, compatible with the subcloning data, is proposed. This model involves a gradual increase in the probability of commitment during cell growth in culture and a small number (about seven) of divisions following commitment. The gradual increase in commitment probability is shown to be compatible with the gradual accumulation of a gene product subject to autogenous regulation.
D002454:Cell Differentiation; D002455:Cell Division; D002999:Clone Cells; D005347:Fibroblasts; D008954:Models, Biological