Enhancement of bleomycin activity by 3-aminobenzamide, a poly (ADP-ribose) synthesis inhibitor, in vitro and in vivo.
A series of poly (ADP-ribose) synthesis inhibitors was evaluated for their ability to potentiate the cytotoxicity of bleomycin compared with their inhibition of poly(ADP-ribose) synthesis in L1210 cultured cells. Theophylline, nicotinamide, 3-aminobenzamide and thymidine inhibited 70 to 80% of poly(ADP-ribose) synthesis in L1210 cells. The degree of inhibition of poly(ADP-ribose) synthesis by these inhibitors corresponded in general with their potentiating ability of bleomycin cytotoxicity. Among these inhibitors, 3-aminobenzamide significantly potentiated the cytotoxic activity of bleomycin (3.6 fold), but it could not potentiate the cytotoxic activity of other antitumor agents, including nitrosourea and Cis-DDP, in L1210 cells in vitro. Treatment of Ehrlich ascites tumor bearing mice with bleomycin and 3-aminobenzamide produced a synergistic effect. 6-Aminonicotinamide also potentiated the antitumor activity of bleomycin against Ehrlich ascites tumor.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology; D002330:Carmustine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D007939:Leukemia L1210 / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009536:Niacinamide / Q000494:pharmacology; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D013806:Theophylline / Q000494:pharmacology; D013936:Thymidine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D001549:Benzamides; D009702:Nucleoside Diphosphate Sugars; D001761:Bleomycin; D009536:Niacinamide; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D013806:Theophylline; D002330:Carmustine; D013936:Thymidine