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

Journal Article · Sat Jun 01 00:00:00 EDT 1991 · Radiation Research; (United States)

DOI:https://doi.org/10.2307/3577927· OSTI ID:5554170

Arundel-Suto, C M; Scavone, S V; Turner, W R; Suto, M J; Sebolt-Leopold, J S ^[1]

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1. Warner-Lambert Company, Ann Arbor, MI (USA)

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.

• OSTI ID: 5554170
• Journal Information: Radiation Research; (United States), Vol. 126:3; ISSN 0033-7587
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
RADIOSENSITIVITY
ENZYME INHIBITORS
RADIOSENSITIVITY EFFECTS
BIOLOGICAL RECOVERY
CELL KILLING
HAMSTERS
LUNGS
POLYMERASES
X RADIATION
ANIMALS
BODY
ELECTROMAGNETIC RADIATION
ENZYMES
IONIZING RADIATIONS
MAMMALS
NUCLEOTIDYLTRANSFERASES
ORGANS
PHOSPHORUS-GROUP TRANSFERASES
RADIATIONS
RECOVERY
RESPIRATORY SYSTEM
RODENTS
TRANSFERASES
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture