Document Detail

Effect of topoisomerase II inhibitors on hyperthermic cytotoxicity.
MedLine Citation:
PMID:  2838165     Owner:  NLM     Status:  MEDLINE    
Exposure of HeLa or Chinese hamster ovary cells to drugs (novobiocin, nalidixic acid, or oxolinic acid) which inhibit the nuclear enzyme topoisomerase II resulted in a sensitization of both cell lines to hyperthermic heating at 41 and 45 degrees C. Exposure to 0.5 mg/ml novobiocin decreased the reciprocal slope (T0) of the survival curve of HeLa cells heated at 41 and 45 degrees C by a factor of 7.5 and 2.4, respectively. Exposure to 0.5 mg/ml novobiocin decreased the T0 of the survival curve of Chinese hamster ovary cells heated at 41 and 45 degrees C by a factor of 9.8 and 1.8, respectively. Exposure of HeLa cells to 0.5 mg/ml novobiocin delayed thermotolerance development for 1.5 h and depressed by a factor of 27 the survival of cells heated at 45 degrees C once thermotolerance had developed. Coincident with the sensitization to heat-induced cytotoxicity, an enhancement of a heat-induced increase in the total protein mass co-isolating with the nuclei or nuclear matrices from heated cells was observed. A log-linear correlation was found between the reduction in cell survival and the relative nuclear matrix protein mass increase in cells heated at 41 or 45 degrees C in the presence or absence of these drugs. The results are consistent with the notion that exposure to these drugs disrupts the cell's capacity to regulate nuclear structure and composition, and thus enhances heat-induced cytotoxicity.
R L Warters; L M Brizgys
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  48     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1988 Jul 
Date Detail:
Created Date:  1988-08-11     Completed Date:  1988-08-11     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3932-8     Citation Subset:  IM    
Department of Radiology, University of Utah Health Sciences Center, Salt Lake City 84132.
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MeSH Terms
Cell Line
Cell Survival*
DNA Topoisomerases, Type II / antagonists & inhibitors*
Hela Cells / drug effects
Hot Temperature*
Nalidixic Acid / pharmacology
Novobiocin / pharmacology
Nucleoproteins / metabolism
Ovary / drug effects
Oxolinic Acid / pharmacology
Grant Support
Reg. No./Substance:
0/Nucleoproteins; 14698-29-4/Oxolinic Acid; 303-81-1/Novobiocin; 389-08-2/Nalidixic Acid; EC Topoisomerases, Type II

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