Shimizu T, Kubota M, Tanizawa A, Sano H, Kasai Y, Hashimoto H, Akiyama Y, Mikawa H
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Biochem Biophys Res Commun. 1990 Jun 29;169(3):1172-7. doi: 10.1016/0006-291x(90)92019-v.
Treatment of a human promyelocytic leukemia cell line (HL-60) with etoposide for 3-4 hrs produced an extensive degradation of DNA. Agarose gel electrophoresis showed DNA fragmentation in a nucleosomal ladder pattern. Simultaneous addition of zinc ion (ZnSO4, 1 mM) inhibited DNA fragmentation, although the amount of DNA strand breakage introduced initially by etoposide did not change significantly as measured by the DNA unwinding assay. Furthermore, zinc ion abrogated both the activation of poly(ADP-ribose) synthesis and the morphologic changes characteristic of apoptosis by etoposide. These results suggest that zinc ion inhibits a metabolic process somewhere between initial DNA cleavage through an interference with type II topoisomerase and delayed degradation of cellular DNA to a nucleosome-like pattern.
用依托泊苷处理人早幼粒细胞白血病细胞系（HL-60）3 - 4小时会导致DNA大量降解。琼脂糖凝胶电泳显示DNA呈核小体梯状条带模式断裂。同时添加锌离子（硫酸锌，1 mM）可抑制DNA断裂，尽管通过DNA解旋试验测定，依托泊苷最初引起的DNA链断裂量没有显著变化。此外，锌离子消除了依托泊苷诱导的聚（ADP-核糖）合成激活以及凋亡特征性的形态学变化。这些结果表明，锌离子通过干扰II型拓扑异构酶抑制了从初始DNA切割到细胞DNA延迟降解为核小体样模式之间的某个代谢过程。
