Myers-Robfogel M W, Spataro A C
Cancer Res. 1980 Jun;40(6):1940-3.
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.
由于已证明胞苷核苷酸会影响正常细胞和恶性细胞中唾液酸转移酶的活性，我们研究了1-β-D-阿拉伯呋喃糖基胞嘧啶（阿糖胞苷）的核苷酸[1-β-D-阿拉伯呋喃糖基胞嘧啶5'-单磷酸和1-β-D-阿拉伯呋喃糖基胞嘧啶5'-三磷酸（阿糖胞苷三磷酸）]对唾液酸糖蛋白合成的影响。正常人二倍体成纤维细胞（WI-38细胞）在汇合状态下进行培养，此时合成DNA的细胞少于1%。1-β-D-阿拉伯呋喃糖基胞嘧啶5'-单磷酸对完整细胞的唾液酸转移酶活性和全细胞匀浆转移酶活性均有抑制作用。还测试了合成和降解唾液酸转移酶底物胞苷5'-单磷酸-N-乙酰神经氨酸（CMP-乙酰神经氨酸）的酶是否受到阿糖胞苷核苷酸的抑制。CMP-乙酰神经氨酸的合成受到阿糖胞苷三磷酸的竞争性抑制；然而，当提供阿糖胞苷三磷酸作为底物时，无法检测到CMP-乙酰神经氨酸的形成。与阿糖胞苷三磷酸或1-β-D-阿拉伯呋喃糖基胞嘧啶5'-单磷酸相比，胞苷5'-三磷酸对CMP-乙酰神经氨酸水解的抑制作用更严重。暴露于阿糖胞苷的WI-38细胞汇合培养物中糖蛋白唾液酸含量降低，这表明阿糖胞苷核苷酸可能在细胞内达到足够的浓度，从而影响上述酶系统。
