The Cytostatic Action of Extracellular NAD in Tumour-bearing Mice

Repeated injections of NAD led to a dose-dependent inhibition of cell proliferation in tumour-bearing mice (Ehrlich ascites carcinoma and a murine mastocytoma). NAD proved clearly superior to other adenine nucleotides, including 3′,5′-cyclic AMP. Experiments with differently labelled NAD and studies on HeLa cultures showed that NAD is relatively slowly degraded by extracellular enzymes to AMP and adenosine, which probably represents the true cytostatic agent. The superiority of NAD in vivo to other adenine nucleotides and to adenosine itself can be explained by the rate-limiting hydrolysis of NAD to AMP with a sustained production of cytostatic concentrations of adenosine. This may represent a new kind of “poisoning” by a potentially cytostatic compound brought about by the action of extracellular enzymes.