pH as a determinant of cellular growth and contact inhibition.

1. Both the growth rate and the maximum population density of several normal, virus-transformed, and cancer cells were markedly pH-dependent; the optimum varied from pH 6.9 to 7.8. At the optimum pH, some diploid human cells attained population densities comparable to those of cancer or virus-transformed cells. Contact inhibition of growth is facilitated by repeated fluctuations of pH in nonphysiological ranges, and may not be an intrinsic and necessary attribute of diploid cells in culture. 2) At pH 8.3, at which there was little or no cellular multiplication, the protein content per cell increased 2- to 5-fold over a period of 10-16 days, and was slowly reversed to normal concentrations on restoration of pH to the optimal range. 3) Uridine uptake by contact-inhibited human cell cultures was stimulated by refeeding with salt solution, and to the same extent as by complete (serum-supplemented) growth medium; that immediate increase did not involve the reinitiation of cellular growth and multiplication. Contact inhibition was, however, reversed in 2-4 days by an appropriate increase in the serum concentration of the medium.