The potentiation of the antitumor activity but not toxicity of bleomycin by 3-aminobenzamide.
Our previous studies have demonstrated that 3-aminobenzamide (3AB), an inhibitor of adenosine diphosphate-ribosyl transferase (ADPRT) could enhance the cytotoxicity (in vitro) and antitumor activity (in vivo) of bleomycin (BLM) A5 and peplomycin (PEP) against S-180, hepatoma and Ehrlich ascites carcinoma (EAC). In this study, it was shown that the inhibition rates (INR's) of S-180 in two experiments were increased from 42.5 and 46.1% to 66.2 and 75.9% when BLM 2.5 mg/kg/day x 8 was combined with 3AB 385.4 mg/kg/day x 8, while the decrease of body weight could not be enhanced. BLM at a dose of 5 mg/kg/day x 8 gave INR's of 64.8 and 75%, similar to the combined group but decreased the body weight more significantly. However, the addition of 3AB 385.4 mg/kg/day to BLM did not increase the acute toxicity of BLM alone. There was no significant difference of change of the body weight and subacute toxicity between the BLM and BLM + 3AB group. There was no difference of peripheral blood white cell count and the pathomorphological and ultrastructural change, wet weight and hydroxyproline content (to reflect the collagen content) of the lung of the mice between BLM alone and BLM + 3AB group. Therefore, the study provided experimental evidences for the reasonable use of nontoxic ADPRT inhibitors in adjunct to the chemotherapy of BLM in cancers.
Pan
Q C
QC
Cancer Institute, Sun Yat-sen University of Medical Sciences, Guangzhou, P.R. China.
Guo
H Y
HY
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001761:Bleomycin / Q000627:therapeutic use* / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006909:Hydroxyproline / Q000032:analysis; D008168:Lung / Q000032:analysis / Q000187:drug effects / Q000473:pathology; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009929:Organ Size / Q000187:drug effects; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D001761:Bleomycin; C025160:3-aminobenzamide; D006909:Hydroxyproline