GROWTH-PROMOTING ACTION OF ADENOSINE-CONTAINING DINUCLEOTIDE ON NEUROBLASTOMA-CELLS - DETECTION OF ADENOSINE-CYTIDINE DINUCLEOTIDE (APCP) IN NEUROFIBROMA (NF1) EXTRACTS

Neurofibroma type 1 tissue was investigated for the presence of growth -promoting activity on human neuroblastoma cells. The activity was iso lated by gel filtration and reversed-phase column chromatographs from neurofibroma type 1 extracts. An adenosine-containing dinucleotide (ad enylyl(3'-5')cytidine-3'-phosphate) was identified as one of the major components of the activities by its enzymatic fragmentation and liqui d chromatography/mass spectrometry. Synthetic adenosine-containing din ucleotide derivatives such as cytidyl(3'-5')adenosine, cytidyl(2'-5')a denosine, adenylyl(3'-5')cytidine, and adenylyl(2'-5')cytidine showed a similar action. Cytidyl(3-5')adenosine, cytidyl(2'-5')adenosine, and adenylyl(2'-5')cytidine, which are able to release a free adenosine t hrough enzymatic hydrolysis, in particular elicited a strong activity corresponding to that of adenosine with the highest action. These resu lts suggest that neuroblastoma cells are able to use adenosine-contain ing dinucleotides as well as mononucleotides for their survival and pr oliferation.