Studies on the mechanism of cytotoxicity of 3-deazaguanosine in human cancer cells.
The mechanism of toxicity of 3-deazaguanosine was studied in a number of human tumor cell lines by determination of the effects of various purine compounds on the growth of the cells in the presence of the drug and by studies of the effects of 3-deazaguanosine on the metabolism of radiolabeled precursors in these cells. The drug was found to be toxic to all of the cell lines tested. The toxicity was reversible with removal of the drug. None of the purine bases tested could restore normal growth after 48 h exposure to 3-deazaguanosine; the bases were more effective in preventing cytotoxicity when added simultaneously with the drug. Metabolic studies indicated decreased synthesis of DNA, variable inhibition of de novo purine synthesis, and complete inhibition of the enzyme guanosine monophosphate reductase by 3-deazaguanosine.
D000225:Adenine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005561:Formates / Q000378:metabolism; D050899:GMP Reductase; D006147:Guanine / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D011687:Purines / Q000494:pharmacology
D005561:Formates; D011687:Purines; D006151:Guanosine; C010568:3-deazaguanosine; D006147:Guanine; D004247:DNA; D009247:NADH, NADPH Oxidoreductases; D050899:GMP Reductase; D000225:Adenine