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The effects of benzamide ADP-ribosyl transferase inhibitors on cell survival and DNA strand-break repair in irradiated mammalian cells.

Abstract
We have recently shown that 3-acetamidobenzamide (3-AAB), a highly effective inhibitor of ADP-ribosyl transferase (ADPRT), can act as a post-irradiation (electrons) sensitizer on the mouse lymphoma cell lines L5178Y R and S. We have now shown that this compound sensitizes human derived skin fibroblasts but to a lesser extent. Fibroblasts derived from normal, Friedreich's ataxia, and ataxia-telangiectasia individuals were equally sensitized by 3-AAB to electron radiation. 3-AAB was also effective in sensitizing the mouse lymphoma lines to fast neutron irradiation. In addition DNA strand break repair was retarded as had been found after electron irradiation. 3-Nitrobenzamide is structurally a potentially dual action radiation sensitizer with electron affinic and ADPRT inhibitory properties. It is a weaker inhibitor of ADPRT compared to 3-AAB, and results in a smaller sensitization of mouse lymphoma cells in air. However, a much greater sensitization is achieved in anoxia. This greater sensitization appears to be a synergistic rather than an additive combination of its electron affinic and ADPRT inhibitory properties.
AuthorsA M George, J Lunec, W A Cramp, S Brennan, P D Lewis, W J Whish
JournalInternational journal of radiation biology and related studies in physics, chemistry, and medicine (Int J Radiat Biol Relat Stud Phys Chem Med) Vol. 49 Issue 5 Pg. 783-98 (May 1986) ISSN: 0020-7616 [Print] England
PMID3009343 (Publication Type: Journal Article)
Chemical References
  • Benzamides
  • 3-acetamidobenzamide
  • Poly(ADP-ribose) Polymerases
  • Nucleotidyltransferases
Topics
  • Animals
  • Benzamides (pharmacology)
  • Cell Survival (drug effects)
  • DNA Repair (drug effects)
  • Humans
  • Leukemia L5178 (genetics)
  • Mice
  • Neutrons
  • Nucleotidyltransferases (antagonists & inhibitors)
  • Poly(ADP-ribose) Polymerases
  • Skin (cytology, radiation effects)
  • Time Factors

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