Inhibitors of Poly(ADP-ribose) Synthetase Enhance the Cytotoxicity of 42°C and 45°C Hyperthermia in Cultured Chinese Hamster Cells

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Abstract
Two inhibitors of poly(ADP-ribose) synthetase, 5-methylnicotinamide and m-methoxybenzamide, enhanced the cytotoxicity of 42°C and 45°C hyperthermia in cultured Chinese hamster V79 cells. The inhibitors showed minimal toxicity for cells treated at 37°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°C heat shock, and after 50 and 100 min exposures to 42°C. When present during heating at 42°C, the inhibitors reduced the shoulder of the 42°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.