Effect of poly(adenosine diphosphate-ribose) polymerase inhibitors on neocarzinostatin-induced G2 delay in HeLa-S3 cells.
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.
Iseki
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Mori
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D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004260:DNA Repair; D006367:HeLa Cells / Q000201:enzymology; D006801:Humans; D009244:NAD+ Nucleosidase / Q000037:antagonists & inhibitors*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis; D013806:Theophylline / Q000494:pharmacology; D013936:Thymidine / Q000494:pharmacology; D009353:Zinostatin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D002110:Caffeine; D009353:Zinostatin; D013806:Theophylline; D011065:Poly(ADP-ribose) Polymerases; D009244:NAD+ Nucleosidase; D013936:Thymidine