APOPTOSIS INDUCED BY DNA TOPOISOMERASE-I AND TOPOISOMERASE-II INHIBITORS IN HUMAN LEUKEMIC HL-60 CELLS

被引：90

作者：

SOLARY, E ^{[1
]}

BERTRAND, R ^{[1
]}

POMMIER, Y ^{[1
]}

机构：

[1] UNIV MED,ONCOHEMATOL LAB,DIJON,FRANCE

来源：

LEUKEMIA & LYMPHOMA | 1994年 / 15卷 / 1-2期

关键词：

HL-60; CELLS; APOPTOSIS; DNA TOPOISOMERASE INHIBITORS; ETOPOSIDE (VP-16); ADRIAMYCIN; CAMPTOTHECIN; LEUKEMIA; DNA DAMAGE; CELL CYCLE;

D O I：

10.3109/10428199409051674

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The induction of apoptosis following topoisomerase inhibitors proceeds in at least three distinct steps: (1) induction of cleavable complexes (potentially lethal damage), (2) topoisomerase-induced DNA damage, and (3) a presently unknown sequence of events that must either lead to cell cycle arrest (G2-block, differentiation) or apoptosis. DNA degradation provides a convenient way to quantify apoptosis in HL-60 cells. Extensive apoptosis can be induced rapidly in undifferentiated HL-60 cells without prevention by cycloheximide or actinomycin D. Therefore, HL-60 cells appear to express constitutively the apoptotic machinery that may be kept under control of a yet unknown repressor. The absence of the tumor suppresser p53 and the presence of bcl-2 are in contrast with the sensitivity of these cells to apoptosis. Agents that modify chromatin structure (zinc, poly[ADPribose] inhibitors, spermine) can block DNA fragmentation without affecting cell survival. By contrast macrophagelike differentiation by phorbol esters suppresses apoptosis without affecting topoisomerase-induced DNA damage. Better understanding of the apoptotic regulation in the widely used and characterized HL-60 cell line should allow the identification of new mechanisms and parameters of cellular sensitivity and resistance to the cytotoxic activity of anticancer agents.

引用

页码：21 / 32

页数：12

共 143 条

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