Adenosine-diphosphoribosyltransferase inhibitors can protect against or potentiate the cytotoxicity of S-phase acting drugs.
We have investigated the effect of inhibitors of ADP-ribosyltransferase on the cytotoxicity of a range of S-phase acting drugs. Co-administration of 3 mM 3-aminobenzamide (3AB) potentiated the cytotoxicity of TG 2-fold, but had no effect on the cytotoxicity of HU, FdUrd or araC. Higher concentrations of benzamides (e.g. 10-20 mM 3AB) produced a G1-specific cell cycle blockade. This treatment prevented cells entering S-phase DNA synthesis and consequently protected against the cytotoxicity of the same S-phase acting drugs. Thus, using different treatment regimens with 3AB, it was possible to either potentiate or protect against the cytotoxicity of TG.
D001549:Benzamides / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006918:Hydroxyurea / Q000494:pharmacology; D007399:Interphase / Q000187:drug effects*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013866:Thioguanine / Q000494:pharmacology
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D003561:Cytarabine; C025160:3-aminobenzamide; D013866:Thioguanine; D006918:Hydroxyurea