DIFFERENTIAL MODULATION OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE METABOLISM BY HYDROXYUREA IN HUMAN-LEUKEMIC CELL-LINES
DIFFERENTIAL MODULATION OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE METABOLISM BY HYDROXYUREA IN HUMAN-LEUKEMIC CELL-LINES
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DOI：
10.1016/0006-2952(88)90438-8
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发表时间：
1988-05-01
影响因子：
5.8
通讯作者：
MIKAWA, H
中科院分区：
文献类型：
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作者：
KUBOTA, M;TAKIMOTO, T;MIKAWA, H
羟基脲（HU）调节1-β-研究了人白血病细胞系中D-阿拉伯呋喃糖基胞嘧啶（Ara-C）的代谢。HL-60细胞暴露于1 mM HU可使Ara-CTP的积累增加2.5倍，而HU对CEM细胞中Ara-C的代谢没有显著影响。此外，两种腺嘌呤核苷，脱氧腺苷（dAdo）和9-β-腺苷（9-β-dAdo），已知被脱氧胞苷（dCyd）激酶激活的D-阿拉伯呋喃糖基腺嘌呤（Ara-A）作为Ara-C，在加入HU后仅在HL-60细胞中被更有效地磷酸化。但HU诱导的细胞内dCTP和TTP池的变化，即dCTP减少和TTP增加，在两种细胞系中是相同的。最后，在正常培养条件下，HL-60细胞中的dCyd产量至少高3至4倍，并被HU给药显著抑制。这些结果表明，通过HU调节Ara-C代谢发生在dCyd激酶水平，通过调节从头dCyd生成。
The ability of hydroxyurea (HU) to modulate 1-.beta.-D-arabinofuranosylcytosine (Ara-C) metabolism was investigated in human leukemic cell lines. Exposure of HL-60 cells to 1 mM HU enhanced the accumulation of Ara-CTP up to 2.5-fold, whereas HU did not have significant effects on Ara-C metabolism in CEM cells. In addition, two adenine nucleosides, deoxyadenosine (dAdo) and 9-.beta.-D-arabinofuranosyladenine (Ara-A), which are known to be activated by deoxycytidine (dCyd) kinase as Ara-C, were more effectively phosphorylated after the addition of HU only in HL-60 cells. However, the changes of intracellular dCTP and TTP pools induced by HU, i.e. decrease in dCTP and incrase in TTP, were the same in both cell lines. Finally, dCyd production under normal culture conditions was at least 3- to 4-fold higher in HL-60 cells and was inhibited significantly by HU administration. These results suggest that the modulation of Ara-C metabolism by HU occurs at the level of dCyd kinase through the regulation of de novo dCyd generation.