Alternative modes of population growth inhibition in a human lymphoid cell line growing in suspension

Abstract

Using a human lymphoid cell line grown under continuous culture conditions, two distinct plateau states were induced, either by lack of sufficient medium-supplied nutrient, or by other unknown mechanisms dependent on cell density. Flow microfluorometric measurements show that growth arrest due to nutritional insufficiency results in an accumulation of cells with G1 DNA content. In contrast, growth arrest due to high cell density is not associated with an altered distribution of cells with respect to DNA content as the population progresses from exponential to plateau state growth. Cell size decreases with progression of the plateau state induced by either type of growth arrest. Cells in a plateau state induced by high cell density utilize glucose and incorporate exogenous amino acid into protein at approximately the same rate as exponential cells. Proliferating, high cell density, plateau state cells have cell cycle phase durations similar to exponential cells. The stable, plateau state cell density is maintained by cell loss. No stable, unbound growth inhibitory factor was found in the medium of density-inhibited plateau state cultures.