Characterization of adenosine-induced cytostasis in melanoma cells.
Relative to lymphoid cells and normal fibroblasts, mouse melanoma cells (B16) were moderately sensitive to adenosine, with 80% growth inhibition being observed at 50 micro M adenosine instead of at 5 micro M as was reported with lymphoid cells or 400 micro M as 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. N6,O2-Dibutyryladenosine-cyclic-3':5' phosphate and polyadenylic acid were ineffective as growth inhibitors, whereas guanosine exhibited potent growth-inhibiting properties. Homocysteine thiolactone enhanced the cytotoxicity of adenosine but not guanosine; adenosine relieved the cytotoxicity of guanosine. These observations indicated that the two purine nucleosides were exerting their growth-inhibiting effects by different mechanisms. Uridine did not relieve adenosine-induced cytostasis, but at 50 micro M adenosine enhanced the incorporation of [3H]uridine into RNA. This suggested that the uridine phosphate pools were depleted at low adenosine concentrations and that exogenous adenosine influences the availability of pyrimidines.
D000241:Adenosine / Q000494:pharmacology*; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D006151:Guanosine / Q000494:pharmacology; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008745:Methylation; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D011743:Pyrimidines / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D014529:Uridine / Q000494:pharmacology
D058892:Adenosine Deaminase Inhibitors; D011743:Pyrimidines; D012334:RNA, Neoplasm; D006710:Homocysteine; D006151:Guanosine; C007957:homocysteine thiolactone; D000241:Adenosine; D014529:Uridine