Oxygen availability as a control factor in the density-dependent regulation of protein synthesis in cell culture.

Dilution of a density-inhibited Arachis culture results in a 10-fold increase in capacity for protein synthesis during the first 2 h after dilution. The limitation in the density-inhibited state is not inadequate nutrition, inappropriate pH, or a diffusible inhibitor as the dilution can be carried out in medium obtained by filtration of 14-day cells. The respiratory rate of the culture increases 2-fold immediately after dilution and the ATP level increases 3-fold during the 2-h period subsequent to dilution. These observations suggest that the initial function activated by dilution is an increased availability of oxygen and that this increase in oxygen provides an increased level of ATP, finally resulting in an increased rate of protein synthesis. This idea is further supported by the finding that both the increase in cellular ATP and the acceleration of the rate of protein synthesis can be obtained in dense culture, in the absence of dilution, by maintaining the cells for 2 h under oxygen.