Summary
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.
Similar content being viewed by others
References
Chen G, Pan QC (1985) Enhancement of antitumor activity of bleomycin A5 by 3-aminobenzamide in vitro and in vivo. Acta Pharm Sinica 20: 331
Chen G, Pan QC (1987) Enhanced growth-inhibiting effect of bleomycin A5 by inhibitors of poly (ADP-R) synthetase on EAC in vitro and in vivo. Science Bulletin 32: 1502
Chen G, Pan QC (1988) Potentiation of antitumor effect of blcomycin by nicotinamide in vivo. Chin J Pharmacol Toxicol 2: 69
Durkacz BW, Omidiji O, Gray DA, Shall S (1980) (ADP-ribose)n participates in DNA excision repair. Nature 283: 593
Erlichman C, Hanada P, Wu A (1984) Enhanced cytotoxicity of cisplatin by 3-aminobenzamide. Proc Am Assoc Cancer Res 25: 368
Goldstein RS Mayor GH (1983) The nephrotoxicity of cisplatin. Life Sci 32: 685
Kawamitsu H, Miwa M, Tanaka Y, Sakamoto H, Terada M, Hoshi A, Sugimura T (1982) Inhibitors of poly (adenosine diphosphate ribose) polymerase potentiate the antitumor activity of bleomycin against Ehrlich ascites carcinoma. J Pharmacol Dyn 5: 900
Mandel P, Okazaki H, Niedergang C (1982) Poly (adenosine diphosphate ribose). In: Cohn WE (ed) Progress in nucleic acid research and molecular biology. Academic Press, New York, pp 1–51
Masuda H, Hamilton TC, Young RC, Ozols RF (1986) Increased DNA repair in human ovarian cancer cell lines with induced resistance to cisplatin or melphalan. Proc Am Assoc Cancer Res 27: 264
Newman RA, Khokhar AR, Sunderland BA, Traris EL, Bulger RE (1986) A comparison in rodents of renal and intestinal toxicity of cisplatin and a new water-soluble antitumor platinum complex: N-methyl-iminodiacetate-diaminocyclohexane platinum. Toxicol Appl Pharmacol 84: 454
Rozencweig M, Von Hoff DD, Abele R, Muggia FM (1981) Cisplatin. In: Pinedo HM (ed) EORTC Cancer chemotherapy annual 3. Excerpta Medica, Amsterdam, pp 120–132
Schein PS, Cooney DA, Vermon ML (1967) The use of nicotinamide to modify the toxicity of streptozotocin diabetes without loss of antitumor activity. Cancer Res 27: 2324
Yamamoto H, Okamoto K (1982) Poly (ADP-ribose) synthetase inhibitors enhance streptozotocin-induced killing of insulinoma cells by inhibiting the repair of DNA strand breaks. FEBS Lett 145: 298
Zwelling LA, Anderson T, Kohn KW (1979) DNA-protein and DNA interstrand cross-linking by cis- and trans-platinum (II) diamminedichloride in L1210 mouse leukemia cells and relation to cytotoxicity. Cancer Res 39: 365
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chen, G., Pan, Qc. Potentiation of the antitumor activity of cisplatin in mice by 3-aminobenzamide and nicotinamide. Cancer Chemother. Pharmacol. 22, 303–307 (1988). https://doi.org/10.1007/BF00254236
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00254236