Potentiation of the antitumor activity of cisplatin in mice by 3-aminobenzamide and nicotinamide.
3-Aminobenzamide (3AB) and nicotinamide (NA), inhibitors of adenosine-ribose transferase (ADPRT), potentiated the antitumor activity of cisplatin (DDP) on Ehrlich ascites carcinoma in mice. The mean survival times of the mice increased from 21.2-37.0 days in DDP-treated groups to 47.0-54.6 days in mice treated with DDP plus NA or 3AB. These drugs also potentiated DDP antitumor activity on sarcoma 180, with the inhibition rates increasing from 12.4%-20.8% in groups treated daily with DDP to 29.8%-46.4% in those treated with DDP plus NA or 3AB; however, neither 3AB nor NA alone showed any antitumor activity. The single-dose lethality of DDP on mice was partially reversed by either NA or 3AB. The pathological study revealed that the morphologic changes in the proximal tubules 1 month after a single dose of DDP (10 mg/kg) were partially prevented by a single protective dose (5 mmol/kg) of NA or 3AB. Our results suggest that the combination of DDP with ADPRT inhibitors might be used clinically in the future.
Chen
G
G
Department of Anticancer Drug Research, Sun Yat-sen University of Medical Sciences, Guangzhou, People's Republic of China.
Pan
Q C
QC
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D001549:Benzamides / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D008297:Male; D051379:Mice; D009336:Necrosis; D009536:Niacinamide / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012510:Sarcoma 180 / Q000473:pathology
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009536:Niacinamide; C025160:3-aminobenzamide; D002945:Cisplatin