In vitro cytotoxic and biochemical effects of 5-aza-2'-deoxycytidine.
The in vitro effect of 5-aza-2'-deoxycytidine (5-aza-CdR) on cytotoxicity and macromolecular synthesis in A(T1)C1-3 hamster fibrosarcoma cells was investigated. The in vitro concentrations that produce 50% cell kill for 5-aza-CdR were about 1.0 and 0.01 microng/ml for a 2- and 24-hr exposure, respectively. 5-aza-CdR inhibited the growth of the fibrosarcoma cells by 40% at a concentration of 0.05 microng/ml. Deoxycytidine, but not cytidine, was a potent antagonist of the cytotoxicity produced by 5-aza-CdR. At cytotoxic concentrations 5-aza-CdR did not appear to inhibit DNA, RNA, or protein synthesis during a 1-hr incubation as measured by the incorporation of radioactive thymidine, uridine,, or leucine into acid-insoluble material. At a concentration of 10 microng/ml, 5-aza-CdR stimulated the incorporation of radioactive thymidine into DNA by more than 50%. These results indicate that 5-aza-CdR is a very potent cytotoxic agent to tumor cells in vitro at concentrations that do not inhibit macromolecular synthesis.
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003562:Cytidine / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D003841:Deoxycytidine; D003562:Cytidine; D001374:Azacitidine