Proliferation of nontransformed cells is inhibited by adenosine metabolite of but not by parental 8-Cl-cyclic AMP.

In this study we evaluated the regulatory effect of 8-Cl-cyclic AMP (cAMP) on the proliferation of nontransformed cells. Our data indicate that similar to the reported inhibitory effect of 8-Cl-cAMP on the proliferation of Molt-4 lymphoma cells, the inhibitory effect of 8-Cl-cAMP on the proliferation of nontransformed fibroblast, myoblast and endothelial cells was dependent on serum or cyclic nucleotide phosphodiesterases and other nucleotide phosphatases. This suggested that the metabolism of 8-Cl-cAMP was required for the inhibition of cell proliferation. In addition, this serum-dependent inhibitory effect of 8-Cl-cAMP was antagonized by the presence of exogenous adenosine deaminase, suggesting that 8-Cl-adenosine was responsible for mediating the serum-dependent inhibitory effect of 8-Cl-cAMP on these cells. This idea was supported further by the ability of 8-Cl-adenosine to duplicate the inhibitory effect of 8-Cl-cAMP on cell proliferation in defined medium.