1-beta-D-arabinofuranosylcytosine nucleotide inhibition of sialic acid metabolism in WI-38 cells.
Because cytidine nucleotides have been demonstrated to affect activity of sialytransferases of both normal and malignant cells, we have investigated the effects of nucleotides of 1-beta-D-arabinofuranosylcytosine (ara-C) [1-beta-D-arabinofuranosylcytosine 5'-monophosphate and 1-beta-D-arabinofuranosycytosine 5'-triphosphate (ara-CTP)] on synthesis of sialoglycoproteins. Normal human diploid fibroblasts (WI-38 cells) were used in culture at confluency, when fewer than 1% of the cells were synthesizing DNA. 1-beta-D-Arabinofuranosylcytosine 5'-monophosphate was inhibitory to both sialytransferase activity of the intact cell and total cell homogenate transferase activity. The enzymes which synthesize and degrade the substrate of sialyltransferases, cytidine 5'-monophosphate-N-acetylneuraminic acid (CMP-AcNeu), were also tested for inhibition by nucleotides of ara-C. Synthesis of CMP-AcNeu was competitively inhibited by ara-CTP; however, formation of CMP-AcNeu when ara-CTP was supplied as substrate could not be detected. Hydrolysis of CMP-AcNeu was inhibited more severely by cytidine 5'-triphosphate than by ara-CTP or 1-beta-D-arabinofuranosylcytosine 5'-monophosphate. Confluent cultures of WI-38 cells exposed to ara-C have decreased amounts of glycoprotein sialic acid, suggesting that ara-C nucleotides may reach sufficient intracellular concentrations to affect the enzyme systems described.
D001085:Arabinofuranosylcytosine Triphosphate / Q000494:pharmacology*; D001088:Arabinonucleotides / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured / Q000378:metabolism; D003561:Cytarabine / Q000494:pharmacology; D003568:Cytidine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D003597:Cytosine Nucleotides / Q000494:pharmacology*; D006801:Humans; D012794:Sialic Acids / Q000378:metabolism*; D012799:Sialyltransferases / Q000378:metabolism*; D014166:Transferases / Q000378:metabolism*
D001088:Arabinonucleotides; D003597:Cytosine Nucleotides; D012794:Sialic Acids; D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate; C024888:1-beta-D-arabinofuranosylcytosine 5'-monophosphate; D014166:Transferases; D012799:Sialyltransferases; D003568:Cytidine Monophosphate