Cell cycle effects of the novel topoisomerase I inhibitor NU/ICRF 505 in a panel of Chinese hamster ovary cell lines

被引:6
作者
Macpherson, JS [1 ]
Cummings, J [1 ]
Meikle, I [1 ]
Miller, EP [1 ]
Smyth, JF [1 ]
机构
[1] WESTERN GEN HOSP,IMPERIAL CANC RES FUND,MED ONCOL UNIT,EDINBURGH EH4 2XU,MIDLOTHIAN,SCOTLAND
关键词
anthracenyl-amino acids; topoisomerase I; NU/ICRF; 505; cell cycle; CHO cells;
D O I
10.1016/S0959-8049(96)00454-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The effect of the novel topoisomerase I inhibitor NU/ICRF 505 (20 mu M, approximate IC50 concentration) on the cell cycle was studied by flow cytometry in four Chinese hamster ovary (CHO) cell lines. Postdrug treated cells were incubated with optimal concentrations of cytochalasin B to prevent re-entry of daughter cells into the cell cycle. NU/ICRF 505 had no significant effect on cell cycle distribution in the parent cell line (CHO-K1) and two mutants hypersensitive to topo II inhibitors (ADR-1, ADR-3), all of which express similar levels of topo I protein. In the drug-resistant variant ADR-r, which overexpresses topo I 2-fold, a significant accumulation of cells in G(1) phase was recorded. These results are broadly consistent with the cell cycle effects expected in CHO cells by a classic topo I poison (camptothecin) and add weight to the view that NU/ICRF 505 induces cell death primarily through topo I inhibition. (C) 1997 Elsevier Science Ltd.
引用
收藏
页码:280 / 283
页数:4
相关论文
共 21 条
[1]  
CORTES F, 1994, CANC CHEMOTHER PHARM, V34, P441
[2]  
Cummings J., 1996, Proceedings of the American Association for Cancer Research Annual Meeting, V37, P358
[3]  
CUMMINGS J, 1995, CANCER CHEMOTH PHARM, V37, P103
[4]   CYTOGENETIC EVALUATION OF THE MECHANISM OF CELL-DEATH INDUCED BY THE NOVEL ANTHRACENYL-AMINO ACID TOPOISOMERASE-II CATALYTIC INHIBITOR NU/ICRF-500 [J].
CUMMINGS, J ;
SUMNER, AT ;
SLAVOTINEK, A ;
MEIKLE, I ;
MACPHERSON, JS ;
SMYTH, JF .
MUTATION RESEARCH-GENETIC TOXICOLOGY, 1995, 344 (1-2) :55-62
[5]   Development of anthracenyl-amino acid conjugates as topoisomerase I and II inhibitors that circumvent drug resistance [J].
Cummings, J ;
Macpherson, JS ;
Meikle, I ;
Smyth, JF .
BIOCHEMICAL PHARMACOLOGY, 1996, 52 (07) :979-990
[6]  
DARPA P, 1990, CANCER RES, V50, P6919
[7]  
DAVIES SM, 1988, J BIOL CHEM, V263, P17724
[8]   ISOLATION AND PARTIAL CHARACTERIZATION OF A MAMMALIAN-CELL MUTANT HYPERSENSITIVE TO TOPOISOMERASE-II INHIBITORS AND X-RAYS [J].
DAVIES, SM ;
DAVIES, SL ;
HALL, AG ;
HICKSON, ID .
MUTATION RESEARCH, 1990, 235 (02) :111-118
[9]   THE CONCENTRATION-DEPENDENT DIVERSITY OF EFFECTS OF DNA TOPOISOMERASE-I AND TOPOISOMERASE-II INHIBITORS ON THE CELL-CYCLE OF HL-60 CELLS [J].
DELBINO, G ;
SKIERSKI, JS ;
DARZYNKIEWICZ, Z .
EXPERIMENTAL CELL RESEARCH, 1991, 195 (02) :485-491
[10]  
DELBINO G, 1990, CANCER RES, V50, P5746