Enhancement of cisplatin (DDP) antitumor activity by 3-aminobenzamide in rat ovarian tumors sensitive and resistant to DDP in vivo.

A cisplatin (DDP)-resistant rat ovarian tumor cell line (O-342/DDP) and its parental sensitive counterpart (O-342) were used to investigate the combination effect of DDP plus 3-aminobenzamide (3-AB), an inhibitor of adenosine diphosphate ribose transferase (ADPRT). Treatment with six doses of DDP in NMRI nude mice bearing O-342/DDP produced an increase in mean survival of only 1 day over that of controls (P less than 0.05). The addition of nontoxic doses of 3-AB (5 mM/kg x 6) increased the mean survival to 6.4 days compared with that obtained with DDP treatment alone (P less than 0.001). In the sensitive ovarian tumor line (O-342), the combination effect of DDP plus 3-AB was even more impressive: simultaneous treatment of NMRI nude mice bearing O-342 with three doses of DDP plus 3-AB increased the mean survival by 2 weeks and the median survival by 3 weeks over that achieved with DDP treatment alone. Possible mechanisms involved in the potentiation of DDP activity and the possible clinical potential of this combination are discussed.