In vitro biochemical and cytotoxicity studies with 1-beta-D-arabinofuranosylcytosine and 5-azacytidine in combination.
The effect of 1-beta-D-arabinofuranosylcytosine (ara-C) and 5-azacytidine (5-aza-C), alone and in combination, on DNA synthesis and cytotoxicity in hamster fibrosarcoma cells has been studied. After a 2-hr exposure of S-phase cells to ara-C at concentrations of 2 to 200 muM, the cells required about 4 to 6 hr to recover from inhibition of DNA synthesis. When 2 exposures to ara-C were used, maximal cytotoxicity occurred when the 2nd dose of ara-C was administered at the time when the cells recovered from the inhibition of DNA synthesis. When the S-phase cells were exposed to ara-C, the maximal killing effect of 5-aza-C occurred when this agent was administered 6 hr later, at the time when the cells had recovered from the inhibition of DNA synthesis. When S-phase cells were exposed to 5-aza-C, the maximal cell kill produced by ara-C also occurred 5 to 6 hr later. When the S-phase cells were exposed simultaneously to both ara-C and 5-aza-C, significant antagonism with respect to cytotoxicity was observed between these 2 agents. When cells in G1 were exposed to 5-aza-C, the cytotoxicity produced by ara-C on these cells when they entered S phase was additive with respect to the cytotoxicity produced by 5-aza-C exposure alone.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000494:pharmacology*; D002455:Cell Division; D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004338:Drug Combinations; D005354:Fibrosarcoma; D013997:Time Factors
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004338:Drug Combinations; D003561:Cytarabine; D001374:Azacitidine