He Q, Xu Y H
Research Laboratory of Blood Physiology, Hunan Medical University, Changsha 410078.
Hunan Yi Ke Da Xue Xue Bao. 2000 Feb 28;25(1):1-5.
To study the effect of 4-methylhistamine on cytotoxicity of Ara-C for HL-60 leukemia cells in vitro.
Proliferation of HL-60 cells was determined by semi-solid colony culture and 3H-TdR incorporation. The typical NBT reduction was used to check cell differentiation. Intracellular cAMP and calcium concentration were determined by high pressure liquid chromatography(HPLC) and fluorescence method, respectively.
When HL-60 cells were pretreated with 10(-8) mol.L-1 4-MH for 24 hrs, the cytotoxicity of Ara-C[10(-8)-10(-4)mol.L-1] for HL-60 leukemia cells was significantly decreased both in liquid and semisolid culture. The result of colony counting indicated that the IC50 for HL-60 cells were 1.68 x 10(-6)mol.L-1 with 4-MH pretreatment nad 2.14 x 10(-8)mol.L-1 without 4-MH pretreatment, respectively. Therefore, the potency of Ara-C was reduced nearly 80 times according to IC50 doses. It is interesting that 10(-6)mol.L-1 ranitidine, an antagonist of H2 receptor, can elaborate the negative effect of 4-MH on cytotoxicity of Ara-C for HL-60 cells.
The dose of Ara-C should be adequately increased, or Ara-C should be used with H2 receptor antagonist such as ranitidine when treating myeloid leukemia patients.
研究4-甲基组胺对阿糖胞苷（Ara-C）体外杀伤HL-60白血病细胞细胞毒性的影响。
采用半固体集落培养和3H-TdR掺入法检测HL-60细胞增殖。用经典的NBT还原法检测细胞分化。分别采用高压液相色谱法（HPLC）和荧光法测定细胞内cAMP和钙浓度。
当HL-60细胞用10^(-8)mol·L^(-1) 4-甲基组胺（4-MH）预处理24小时后，阿糖胞苷[10^(-8)-10^(-4)mol·L^(-1)]在液体和半固体培养中对HL-60白血病细胞的细胞毒性均显著降低。集落计数结果表明，经4-MH预处理后HL-60细胞的半数抑制浓度（IC50）为1.68×10^(-6)mol·L^(-1)，未经4-MH预处理时为2.14×10^(-8)mol·L^(-1)。因此，根据IC50剂量，阿糖胞苷的效力降低了近80倍。有趣的是，H2受体拮抗剂10^(-6)mol·L^(-1)雷尼替丁可增强4-MH对阿糖胞苷杀伤HL-60细胞细胞毒性的负面影响。
在治疗髓系白血病患者时，应适当增加阿糖胞苷的剂量，或与雷尼替丁等H2受体拮抗剂联合使用阿糖胞苷。
