Poly(ADP-ribosylation) reduces the steady-state level of breaks in DNA following treatment of human cells with alkylating agents

Carcinogenesis. 1984 Jan;5(1):117-9. doi: 10.1093/carcin/5.1.117.

Abstract

Following treatment of human fibroblasts with dimethyl-sulphate, more breaks persisted in DNA in cells incubated with 3-aminobenzamide, an inhibitor of ADP-ribosyltransferase, than in its absence. This effect of 3-aminobenzamide was more pronounced in non-dividing than in dividing cells. If non-dividing cells were treated with dimethylsulphate and then incubated for a few hours in the absence of 3-aminobenzamide, few breaks were detectable in the DNA. Subsequent addition of 3-aminobenzamide resulted in the reappearance of many breaks in the DNA. These data suggest that continued synthesis of poly(ADP-ribose) reduces the steady state level of breaks during excision repair of alkylation damage. This is probably mediated by the stimulation of DNA ligase activity. Inhibition of poly(ADP-ribose) synthesis with 3-aminobenzamide maintains or restores a higher steady-state level of breaks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / pharmacology*
  • Benzamides / pharmacology
  • Cells, Cultured
  • DNA / metabolism*
  • DNA Repair / drug effects*
  • Humans
  • Nucleoside Diphosphate Sugars / metabolism*
  • Nucleotidyltransferases / antagonists & inhibitors
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly(ADP-ribose) Polymerases

Substances

  • Alkylating Agents
  • Benzamides
  • Nucleoside Diphosphate Sugars
  • Poly Adenosine Diphosphate Ribose
  • 3-aminobenzamide
  • DNA
  • Poly(ADP-ribose) Polymerases
  • Nucleotidyltransferases