Effect of PD 128763, a new potent inhibitor of poly(ADP-ribose) polymerase, on X-ray-induced cellular recovery processes in Chinese hamster V79 cells

• Published in: Radiation research Vol. 126; no. 3; pp. 367 - 371
• Main Authors: Arundel-Suto, C M, Scavone, S V, Turner, W R, Suto, M J, Sebolt-Leopold, J S
• Format: Journal Article
• Language: English
• Published: United States 01-06-1991
• Subjects: 560120 - Radiation Effects on Biochemicals, Cells, & Tissue Culture; ANIMAL CELLS; ANIMALS; Benzamides - pharmacology; BIOLOGICAL RECOVERY; BODY; CELL KILLING; Cell Survival - drug effects; Cell Survival - radiation effects; Cells, Cultured - radiation effects; Cricetinae; Cricetulus; ELECTROMAGNETIC RADIATION; ENZYME INHIBITORS; ENZYMES; HAMSTERS; IONIZING RADIATIONS; Isoquinolines - pharmacology; LUNGS; MAMMALS; NUCLEOTIDYLTRANSFERASES; ORGANS; PHOSPHORUS-GROUP TRANSFERASES; Poly(ADP-ribose) Polymerase Inhibitors; POLYMERASES; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; RADIATIONS; RADIOSENSITIVITY; RADIOSENSITIVITY EFFECTS; RECOVERY; RESPIRATORY SYSTEM; RODENTS; Space life sciences; TRANSFERASES; VERTEBRATES; X RADIATION
• ISSN: 0033-7587; 1938-5404
• DOI: 10.2307/3577927

The modifying effects of PD 128763 (3,4-dihydro-5-methyl-1(2H)-isoquinolinone), a potent inhibitor of poly(adenosine-diphosphate (ADP)-ribose) polymerase, on radiation-induced cell killing were examined in Chinese hamster V79 cells. This compound has an IC50 value against the purified enzyme approximately 50X lower than 3-aminobenzamide (3-AB), a widely used specific inhibitor of the enzyme. Exposure of exponentially growing cells to a noncytotoxic concentration (0.5 mM) of PD 128763 for 2 h immediately following X irradiation increased their radiation sensitivity, modifying both the shoulder and the slope of the survival curve. When recovery from sublethal damage and potentially lethal damage was examined in exponential and plateau-phase cells, respectively, postirradiation incubation with 0.5 mM PD 128763 was found not only to inhibit both these processes fully, but also to enhance further the level of radiation-induced cell killing. This is in contrast to the slight effect seen with the less potent inhibitor, 3-AB. The results presented suggest that the mechanism of radiosensitization by PD 128763 is related to the potent inhibition of poly(ADP-ribose) polymerase by this compound.