Inhibitory effect of 1-beta-D-arabinofuranosylcytosine on the synthesis of phosphatidyl-dCMP.
The synthesis of phosphatidyl-dCMP in mouse thymocytes is inhibited by the antineoplastic agent 1-beta-D-arabinofuranosyl cytosine (AraCyt) 50% inhibition (ID50) being reached at an AraCyt concentration of 0.18 mM. In the same cells, ID50 for DNA synthesis is 0.03 mM. This inhibition is probably mediated by the phosphorylated derivative of AraCyt (aCTP) since the synthesis of phosphatidyl-dCMP from dCTP using permeabilized thymocytes is inhibited by aCTP (ID50 = 0.11 mM). The incorporation of [3H]AraCyt into the organic phase could also be detected, suggesting that this drug may act as a substrate for the enzyme that catalyzes the transfer of dCTP into phosphatidic acid.
D000818:Animals; D003561:Cytarabine / Q000378:metabolism / Q000494:pharmacology*; D003843:Deoxycytidine Monophosphate / Q000031:analogs & derivatives / Q000096:biosynthesis*; D003845:Deoxycytosine Nucleotides / Q000096:biosynthesis*; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D013950:Thymus Gland / Q000378:metabolism*
D003845:Deoxycytosine Nucleotides; C020461:phosphatidyl-dCMP; D003561:Cytarabine; D003843:Deoxycytidine Monophosphate