Chou R H, Chervenick P A
Cell Tissue Kinet. 1985 Jul;18(4):387-97. doi: 10.1111/j.1365-2184.1985.tb00669.x.
The relationships between replicative DNA synthesis and retinoic acid (RA)-induced differentiation of human promyelocytic leukaemic (HL-60) cells are evaluated with the use of Aphidicolin, a specific and reversible inhibitor of DNA polymerase alpha (alpha). Addition of a sublethal concentration of Aphidicolin (0.4 microM) in culture for 3 days suppresses DNA synthesis to a similar level of the resting stage (day 8) in control cultures. DNA synthesis is reactivated to the level observed in the growing stage of control cultures once Aphidicolin is removed after 3 days in culture. The level of DNA synthesis at the early stage of RA-induction (day 3) is suppressed by only 17% when compared to control cultures. The inhibitory effect of Aphidicolin on DNA synthesis in both control cultures and RA-induced cell cultures is similar. However, no reactivation of DNA synthesis is observed after removal of Aphidicolin on day 3 from RA-induced cell cultures. Flow cytometric analysis of DNA content on day 3 reveals that cells accumulate in G1 and early S phases of the cell cycle after exposure to Aphidicolin with or without RA. Of interest is the fact that, while Aphidicolin alone did not induce cells to differentiate, neither did it interfere with RA-induced cell differentiation (the rate of RA-induced cell differentiation in the presence of Aphidicolin is similar to that of RA-treated cultures in the absence of Aphidicolin). These results suggest that the combined use of Aphidicolin and RA may inhibit leukaemic cell proliferation more effectively without causing severe cytotoxicity and without interfering with RA-induced cell differentiation.
利用阿非迪霉素（一种特异性且可逆的DNA聚合酶α抑制剂）评估了复制性DNA合成与维甲酸（RA）诱导的人早幼粒细胞白血病（HL-60）细胞分化之间的关系。在培养物中添加亚致死浓度的阿非迪霉素（0.4 microM）3天，可将DNA合成抑制至与对照培养物静止期（第8天）相似的水平。在培养3天后去除阿非迪霉素后，DNA合成重新激活至对照培养物生长阶段所观察到的水平。与对照培养物相比，RA诱导早期（第3天）的DNA合成水平仅被抑制了17%。阿非迪霉素对对照培养物和RA诱导的细胞培养物中DNA合成的抑制作用相似。然而，在第3天从RA诱导的细胞培养物中去除阿非迪霉素后，未观察到DNA合成的重新激活。第3天对DNA含量进行的流式细胞术分析表明，无论有无RA，暴露于阿非迪霉素后细胞在细胞周期的G1期和早期S期积累。有趣的是，虽然单独使用阿非迪霉素不会诱导细胞分化，但它也不会干扰RA诱导的细胞分化（在存在阿非迪霉素的情况下RA诱导的细胞分化率与在不存在阿非迪霉素的情况下RA处理的培养物相似）。这些结果表明，联合使用阿非迪霉素和RA可能更有效地抑制白血病细胞增殖，而不会引起严重的细胞毒性，也不会干扰RA诱导的细胞分化。
