Analysis of camptothecin resistance in yeast: relevance to cancer therapy

被引:7
作者
Benedetti, P
Benchokroun, Y
Houghton, PJ
Bjornsti, MA
机构
[1] Thomas Jefferson Univ, Dept Biochem & Mol Pharmacol, Philadelphia, PA 19107 USA
[2] CNR, Ist Biol Cellulare, I-00016 Rome, Italy
[3] St Jude Childrens Res Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA
关键词
D O I
10.1016/S1368-7646(98)80037-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The budding yeast Saccharomyces cerevisiae is a well defined genetic system to investigate various aspects of camptothecin (Cpt)-induced cytotoxicity. This antineoplastic agent and its derivatives specifically poison eukaryotic DNA topoisomerase I, the product of the TOPI gene, by stabilizing a covalent enzyme-DNA intermediate. Analyses of various yeast and human top I mutants in yeast strains deleted for TOPI (top Id) have defined amino acid residues critical for enzyme function and Cpt sensitivity. Cpt cytotoxicity is also mediated by the pleiotropic drug resistance network, primarily through the action of an ABC transporter. The potential clinical relevance of these and related studies are discussed.
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页码:176 / 183
页数:8
相关论文
共 52 条
[1]  
ALSNER J, 1992, J BIOL CHEM, V267, P12408
[2]  
[Anonymous], METHOD ENZYMOL
[3]   YEAST MULTIDRUG-RESISTANCE - THE PDR NETWORK [J].
BALZI, E ;
GOFFEAU, A .
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 1995, 27 (01) :71-76
[4]  
Beidler DR, 1996, CANCER RES, V56, P345
[5]  
BENEDETTI P, 1993, CANCER RES, V53, P4343
[7]  
BJORNSTI MA, 1989, CANCER RES, V49, P6318
[8]   YEAST SACCHAROMYCES-CEREVISIAE AS A MODEL SYSTEM TO STUDY THE CYTOTOXIC ACTIVITY OF THE ANTITUMOR DRUG CAMPTOTHECIN [J].
BJORNSTI, MA ;
KNAB, AM ;
BENEDETTI, P .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1994, 34 :S1-S5
[9]  
Bronstein IB, 1996, ONCOL RES, V8, P17
[10]   Mitotic chromosome condensation in the rDNA requires TRF4 and DNA topoisomerase I in Saccharomyces cerevisiae [J].
Castano, IB ;
Brzoska, PM ;
Sadoff, BU ;
Chen, HY ;
Christman, MF .
GENES & DEVELOPMENT, 1996, 10 (20) :2564-2576