Effect of a poly(ADP-ribose) polymerase inhibitor on DNA breakage and cytotoxicity induced by hydrogen peroxide and gamma-radiation

Teratog Carcinog Mutagen. 1996;16(4):219-27. doi: 10.1002/(SICI)1520-6866(1996)16:4<219::AID-TCM3>3.0.CO;2-L.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides / pharmacology*
  • Cell Count
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cells, Cultured
  • DNA / drug effects
  • DNA / radiation effects
  • DNA Damage / drug effects*
  • Dimethyl Sulfoxide / pharmacology
  • Enzyme Inhibitors / pharmacology*
  • Gamma Rays*
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • In Vitro Techniques
  • Leukocytes / drug effects*
  • Leukocytes / radiation effects*
  • Poly(ADP-ribose) Polymerase Inhibitors*

Substances

  • Benzamides
  • Enzyme Inhibitors
  • Poly(ADP-ribose) Polymerase Inhibitors
  • 3-aminobenzamide
  • DNA
  • Hydrogen Peroxide
  • Dimethyl Sulfoxide