1-BETA-D-ARABINOFURANOSYLCYTOSINE NUCLEOTIDE INHIBITION OF SIALIC-ACID METABOLISM IN WI-38 CELLS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (6) , 1940-1943
Abstract
Because cytidine nucleotides affect activity of sialyltransferases of normal and malignant cells, the effects of nucleotides of 1-.beta.-D-arabinofuranosylcytosine (ara-C) [1-.beta.-D-arabinofuranosyl-CMP and 1-.beta.-D-arabinofuranosyl-CTP (ara-CTP)] on synthesis of sialoglycoproteins were studied. Normal human diploid fibroblasts (WI-38 cells) were used in culture at confluency, when < 1% of the cells were synthesizing DNA. 1-.beta.-D-Arabinofuranosyl-CMP was inhibitory to sialytransferase activity of the intact cell and total cell homogenate transferase activity. The enzymes which synthesize and degrade the substrate of sialyltransferases, CMP-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 CTP than by ara-CTP or 1-.beta.-D-arabinofuranosyl-CMP. 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. [The results are discussed in relation to cancer therapy.].

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