The effects of benzamide ADP-ribosyl transferase inhibitors on cell survival and DNA strand-break repair in irradiated mammalian cells.
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.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D007940:Leukemia L5178 / Q000235:genetics; D051379:Mice; D009502:Neutrons; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D011065:Poly(ADP-ribose) Polymerases; D012867:Skin / Q000166:cytology / Q000528:radiation effects; D013997:Time Factors
D001549:Benzamides; C040561:3-acetamidobenzamide; D011065:Poly(ADP-ribose) Polymerases; D009713:Nucleotidyltransferases