Inhibition of growth and DNA synthesis in cell cultures by cyclic AMP.

Cyclic AMP (o-i to 1 mM) was found to inhibit the growth of human liver cells in monolayer cultures. Significant amounts of degradation products were not detected in the medium indicating that the growth-inhibiting effect was associated with the intact cyclic nucleotide. DNA synthesis in the liver cell cultures, as measured by thymidine incorporation into acidinsoluble material, was markedly inhibited by cyclic AMP. RNA and protein synthesis were not significantly affected. Cyclic AMP induced a considerable increase in the cellular uptake of thymidine and uridine from the medium. When the liver cells were incubated in medium containing radioactive cyclic AMP, no labelled cyclic AMP could be detected in the acid-soluble cell fraction by chromatographic analysis. It is suggested that cyclic AMP does not enter the liver cells, but that its action on growth and DNA synthesis is somehow mediated through an interaction with the cell surface.