Characterization of Adenosine-induced Cytostasis in Melanoma Cells1

Relative to lymphoid cells and normal fibroblasta, mouse melanoma cells (B16) were moderately sensitive to adenosine, with 80% growth inhibition being observed at 50 /XMadenosine instead of at 5 fiM as was reported with lymphoid cells or 400 ¡IMas was reported for normal fibroblasts. These differences were not due to adenosine deaminase because lymphoid cells had two to four times more of this activity than did melanoma cells or normal fibroblasts. In melanoma cells, complete adenosine-induced growth inhibition was a gradual process which was observed only after one to two population doublings; after 4 days of treatment, complete recovery was gradual requiring 48 hr. /V6,O2-Dibutyryladenosine-cyclic-3':5' phosphate and polyadenylic acid were ineffective as growth inhibitors, whereas guanosine exhibited potent growth-inhibiting proper ties. Homocysteine thiolactone enhanced the cytotoxicity of adenosine but not guanosine; adenosine relieved the cytotox icity of guanosine. These observations indicated that the two purine nucleosides were exerting their growth-inhibiting effects by different mechanisms. Uridine did not relieve adenosineinduced cytostasis, but at 50 fiM adenosine enhanced the incorporation of [3H]uridine into RNA. This suggested that the uridine phosphate pools were depleted at low adenosine con centrations and that exogenous adenosine influences the avail ability of pyrimidines.