Maehara Y, Kusumoto T, Sakaguchi Y, Kusumoto H, Anai H, Sugimachi K
Cancer Center, Kyushu University Hospital, Fukuoka, Japan.
Anticancer Res. 1989 Jan-Feb;9(1):41-4.
The metabolism of 1-beta-D-arabinofuranosylcytosine (ara-C) and N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC) was studied in Hela cells. After the cells were exposed to ara-C at a concentration of 20 micrograms/ml or BH-AC at 46.5 micrograms/ml for 1, 3, 6, 12 or 24 hr, the level of ara-C was determined using the radioimmunoassay method, and the level of BH-AC and 1-beta-D-arabinofuranosyluracil (ara-U), using high-performance liquid chromatography. In the ara-C-treated cells, the intracellular ara-C increased to 1.26 micrograms/g cells after exposure for 6 hr, and ara-C was rapidly changed to ara-U in the cells and in the medium. In the BH-AC-treated cells, the intracellular BH-AC increased after exposure for 24 hr and BH-AC was gradually converted to ara-C in the cells: the intracellular level of ara-C was only 15% of that of BH-AC after exposure for 24 hr. BH-AC level in the medium persisted for 24 hr, at the initial concentration. Our findings show that BH-AC is stable compared to ara-C and gradually converts to ara-C. This conversion is presumably a critical step in the antineoplastic effect of BH-AC.
在人宫颈癌细胞（Hela细胞）中研究了1-β-D-阿拉伯呋喃糖基胞嘧啶（阿糖胞苷，ara-C）和N4-山嵛酰基-1-β-D-阿拉伯呋喃糖基胞嘧啶（BH-AC）的代谢情况。将细胞分别暴露于浓度为20微克/毫升的阿糖胞苷或46.5微克/毫升的BH-AC中1、3、6、12或24小时后，采用放射免疫分析法测定阿糖胞苷水平，采用高效液相色谱法测定BH-AC和1-β-D-阿拉伯呋喃糖基尿嘧啶（阿糖尿嘧啶，ara-U）水平。在阿糖胞苷处理的细胞中，暴露6小时后细胞内阿糖胞苷增加至1.26微克/克细胞，且阿糖胞苷在细胞和培养基中迅速转变为阿糖尿嘧啶。在BH-AC处理的细胞中，暴露24小时后细胞内BH-AC增加，且BH-AC在细胞中逐渐转化为阿糖胞苷：暴露24小时后细胞内阿糖胞苷水平仅为BH-AC的15%。培养基中BH-AC水平在24小时内维持在初始浓度。我们的研究结果表明，与阿糖胞苷相比，BH-AC更稳定，并逐渐转化为阿糖胞苷。这种转化可能是BH-AC抗肿瘤作用的关键步骤。
