Inhibitors of poly(ADP-ribose) synthetase enhance the cytotoxicity of 42 degrees C and 45 degrees C hyperthermia in cultured Chinese hamster cells.

Abstract

Two inhibitors of poly(ADP-ribose) synthetase, 5-methylnicotinamide and m-methoxybenzamide, enhanced the cytotoxicity of 42 degrees C and 45 degrees C hyperthermia in cultured Chinese hamster V79 cells. The inhibitors showed minimal toxicity for cells treated at 37 degrees C, and did not appreciably alter cellular ATP levels under any of the experimental conditions used. Enhanced cell killing occurred when the inhibitors were added after an acute (5-10 min) 45 degrees C heat shock, and after 50 and 100 min exposures to 42 degrees C. When present during heating at 42 degrees C, the inhibitors reduced the shoulder of the 42 degrees C survival curves but did not appreciably affect the slopes. The results suggest a possible role for poly(ADP-ribose) synthetase in the survival response of V79 cells to hyperthermia.

• Authors: W A Nagle, A J Moss Jr
• Journal: International journal of radiation biology and related studies in physics, chemistry, and medicine (Int J Radiat Biol Relat Stud Phys Chem Med) Vol. 44 Issue 5 Pg. 475-81 (Nov 1983) ISSN: 0020-7616 [Print] England
• PMID: 6315616 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzamides
• Poly(ADP-ribose) Polymerase Inhibitors
• Niacinamide
• 5-methylnicotinamide
• NAD+ Nucleosidase
• 3-methoxybenzamide

Topics

• Animals
• Benzamides (pharmacology)
• Cell Line
• Cell Survival (drug effects)
• Cricetinae
• Cricetulus
• Dose-Response Relationship, Drug
• Hyperthermia, Induced
• NAD+ Nucleosidase (antagonists & inhibitors)
• Niacinamide (analogs & derivatives, pharmacology)
• Poly(ADP-ribose) Polymerase Inhibitors
• Time Factors