The effects of 3',5' adenosine monophosphate on the proliferation of Reuber H35 rat hepatoma cells in vitro.

3',5' Adenosine monophosphate (cAMP) inhibits the proliferation of Reuber H35 rat hepatoma cells at concentrations higher than 10(-5) M. This inhibitory effect can be demonstrated both in exponentially growing monolayer cultures and in single cell clonal growth. The inhibition of the cell proliferation is due to both a short term (division delay) and a long term effect (cytotoxicity). The short term effect seems to be due to cAMP itself as it is potentiated by the phosphodiesterase inhibitor 1-methyl,3-isobutyl xanthine (MIX). The long term effect probably is due to degradation products of the cyclic nucleotide. It is shown by a combination of time lapse cinematography, autoradiography, and flow cytofluorometry that the division delay is due to a prolongation of the S phase with no apparent changes in the duration of the G1 phase. The possible causes of this prolongation of the S phase by cAMP are discussed.