Effect of a poly(ADP-ribose) polymerase inhibitor on DNA breakage and cytotoxicity induced by hydrogen peroxide and gamma-radiation.
The activity of poly(ADP-ribose) polymerase (PARP) is activated upon recognition of DNA strand breaks by its DNA-binding domain and the stimulation of this nuclear enzyme seems to be an early response of cells exposed to a variety of different DNA-damaging agents. In the present work we evaluate the effect of hydrogen peroxide and gamma-radiation on DNA strand breaks in human leukocytes in the presence and in the absence of 3-aminobenzamide (3AB), a potent inhibitor of PARP. Our results have shown differences in the role poly(ADP-ribosyl)ation in the rejoining of DNA strand breaks induced by hydrogen peroxide and gamma-radiation. We observed a PARP-dependent recovery of DNA strand breaks at the incubation time of 20-30 min in leukocytes treated with hydrogen peroxide. The repair of DNA strand breaks induced by gamma-radiation seems to be dependent on oxygen radical scavenging and the stimulation of PARP could be related to the protection of DNA strand breaks from hydroxyl radicals.
Cristóvão
L
L
Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, Portugal.
Rueff
J
J
D001549:Benzamides / Q000494:pharmacology*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005720:Gamma Rays; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects* / Q000528:radiation effects*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D001549:Benzamides; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D004247:DNA; D006861:Hydrogen Peroxide; D004121:Dimethyl Sulfoxide