Potentiation of the antitumor activity of cisplatin in mice by 3-aminobenzamide and nicotinamide

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Abstract
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.