Document Detail

Effect of poly(adenosine diphosphate-ribose) polymerase inhibitors on neocarzinostatin-induced G2 delay in HeLa-S3 cells.
MedLine Citation:
PMID:  2992774     Owner:  NLM     Status:  MEDLINE    
The antitumor antibiotic neocarzinostatin (NCS), which produces single-strand breaks in mammalian cell DNA in vivo, stimulated the activity of chromatin bound enzyme, poly(ADP-ribose) polymerase in HeLa-S3 cells. Because of the possible causal relationship between the poly ADP-ribosylation of chromatin protein and NCS-induced temporary G2 arrest in the cell cycle, several classes of inhibitors of poly(ADP-ribose) polymerase were examined to evaluate the effect on NCS-induced polymerase activity as well as on progression in the cell cycle of synchronized HeLa cells which had been treated with NCS in G2. Compared at the same concentration of 2 mM, the polymerase-inhibiting activity was larger in the order of thymidine, 3-aminobenzamide, nicotinamide, theophylline, and caffeine. Among these agents, caffeine, theophylline, and thymidine caused a reduction in the G2 delay in this order by stimulating the cells to undergo mitosis after NCS treatment. However, 3-aminobenzamide and nicotinamide were poor reducers, if any, of NCS-induced G2 delay. These results suggest that there is not a direct involvement of poly ADP-ribosylation of chromatin protein in the mechanism of NCS-induced G2 delay. The effect of caffeine on G2 delay will probably be independent of its activity as a poly(ADP-ribose) polymerase inhibitor.
S Iseki; T Mori
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  45     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1985 Sep 
Date Detail:
Created Date:  1985-09-30     Completed Date:  1985-09-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4224-8     Citation Subset:  IM    
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MeSH Terms
Antibiotics, Antineoplastic / pharmacology*
Caffeine / pharmacology
Cell Cycle / drug effects
Cells, Cultured
DNA Repair
Hela Cells / enzymology
NAD+ Nucleosidase / antagonists & inhibitors*
Poly(ADP-ribose) Polymerases / analysis,  antagonists & inhibitors*
Theophylline / pharmacology
Thymidine / pharmacology
Zinostatin / pharmacology*
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 50-89-5/Thymidine; 58-08-2/Caffeine; 58-55-9/Theophylline; 9014-02-2/Zinostatin; EC Polymerases; EC Nucleosidase

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