Inhibitors of poly(ADP-ribose) polymerase enhance DNA strand breaks, excision repair, and sister chromatid exchanges induced by alkylating agents

Environ Mutagen. 1983;5(4):515-25. doi: 10.1002/em.2860050402.

Abstract

Benzamide and 3-aminobenzamide, inhibitors of poly(ADP-ribose) polymerase, synergistically enhanced the frequencies of unscheduled DNA synthesis and sister chromatid exchanges in Chinese hamster ovary (CHO) cells treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). These inhibitors also increased methyl methanesulfonate (MMS)- or MNNG-induced DNA strand breaks and significantly retarded the rejoining of strand breaks in CHO and HeLa S3 cells. These results suggest that poly(ADP-ribose) is important in the repair of DNA damage after exposure to alkylating agents and exercises a regulatory role in stabilizing chromatin structure whenever strand breaks occur in DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / toxicity*
  • Animals
  • Benzamides / toxicity*
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Crossing Over, Genetic / drug effects*
  • DNA / isolation & purification
  • DNA / metabolism
  • DNA Repair / drug effects*
  • DNA Replication / drug effects*
  • Drug Synergism
  • Female
  • Kinetics
  • Mutagens / toxicity*
  • NAD+ Nucleosidase / antagonists & inhibitors*
  • Ovary
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Sister Chromatid Exchange / drug effects*

Substances

  • Alkylating Agents
  • Benzamides
  • Mutagens
  • Poly(ADP-ribose) Polymerase Inhibitors
  • benzamide
  • 3-aminobenzamide
  • DNA
  • NAD+ Nucleosidase