Enhancement of bleomycin activity by 3-aminobenzamide, a poly (ADP-ribose) synthesis inhibitor, in vitro and in vivo

Anticancer Res. Mar-Apr 1988;8(2):239-43.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / pharmacology*
  • Bleomycin / pharmacology*
  • Carcinoma, Ehrlich Tumor / pathology
  • Carmustine / pharmacology
  • Cell Survival / drug effects
  • Drug Synergism
  • Female
  • Leukemia L1210 / metabolism
  • Leukemia L1210 / pathology
  • Mice
  • Niacinamide / pharmacology
  • Nucleoside Diphosphate Sugars / biosynthesis*
  • Poly Adenosine Diphosphate Ribose / biosynthesis*
  • Theophylline / pharmacology
  • Thymidine / pharmacology
  • Tumor Cells, Cultured / drug effects

Substances

  • Benzamides
  • Nucleoside Diphosphate Sugars
  • Bleomycin
  • Niacinamide
  • Poly Adenosine Diphosphate Ribose
  • 3-aminobenzamide
  • Theophylline
  • Carmustine
  • Thymidine