Poly(ADP-ribose) synthetase inhibitors increase radiation and thermal sensitivity but do not affect thermotolerance

The effects of 3-aminobenzamide and benzamide (inhibitors of poly(ADP-ribose] synthetase on heat and radiation responses of Chinese hamster V79 cells have been examined. Consistent with earlier reports the inhibitors of poly(ADP-ribose) formation caused radiosensitization and inhibition of repair of radiation-induced potentially lethal damage. Both benzamide and 3-aminobenzamide caused thermosensitization for heating temperatures ranging from 42-45 degrees C. Benzamide had a greater effect than 3-aminobenzamide at equimolar concentrations. Thermosensitization increased with concentration of the inhibitors and was greater for prolonged heating times. While both inhibitors caused thermosensitization, they did not affect the time scale for the development of thermotolerance at 42 degrees C or after acute heating at 45 degrees C. The inhibitors of poly(ADP-ribosylation) radiosensitizers and thermosensitizers may be of use in the treatment of cancer using a combined modality of radiation and hyperthermia.