Cytidine deaminase and the development of resistance to arabinosyl cytosine.
Cytidine deaminase and the development of resistance to arabinosyl cytosine.
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胞苷脱氨酶和阿拉伯糖胞嘧啶抗性的发展。
DOI：
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发表时间：
1971
期刊：
影响因子：
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通讯作者：
P. Burke
中科院分区：
文献类型：
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作者：
C. D. Steuart;P. Burke
阿拉伯糖胞嘧啶（阿糖胞苷：1-β-D-阿拉伯呋喃糖胞嘧啶，“Cytosar”，缩写为 ara-C）治疗人类白血病的有效性与该分子的体外摄取率及其随后的磷酸化有关。在人体中，这种核苷也会迅速脱氨，产生无治疗活性的阿拉伯糖基尿苷2：肝脏和血清中都含有嘧啶核苷脱氨酶3。因此，人血清中未变化的 ara-C 的半衰期很短（约 15 min−1）（参考文献 2）。这些特征表明胞苷脱氨酶与白血病细胞对ara-C的敏感性之间存在关系，我们发现人类白血病的初始治疗反应与细胞内脱氨酶浓度低于无反应者中的脱氨酶浓度相关。此外，在顺序治疗方案中，脱氨酶浓度的增加与肿瘤细胞对ara-C的敏感性显着降低相关。
THE effectiveness of arabinosyl cytosine (cytarabine: 1-β-D-arabinofuranosylcytosine, ‘Cytosar’, abbreviated to ara-C) in the treatment of human leukaemia can be correlated with the rate of uptake of the molecule in vitro1 and its subsequent phosphorylation. In man, this nucleoside is also rapidly deaminated to produce arabinosyl uridine which has no therapeutic activity2: both liver and serum contain pyrimidine nucleoside deaminase3. Consequently the half-life of unchanged ara-C in human sera is brief (about 15 min−1) (ref. 2). These characteristics suggest a relationship between cytidine deaminase and the susceptibility of the leukaemic cell to ara-C, and we have found that initial therapeutic responses in human leukaemia are correlated with lower intracellular concentrations of deaminase than those present in non-responders., Furthermore, in sequential treatment schedules, increasing concentrations of deaminase are associated with markedly reduced susceptibility of the tumour cell to ara-C.