Potentiation of bleomycin cytotoxicity by polyhydric alcohols.
The cytotoxicity of bleomycin (BLM) toward Chinese Hamster V79 and murine leukemia L1210 was extraordinarily potentiated in the presence of glycerol. The synergistic effect of glycerol emerged in combinations with BLM analogs (peplomycin and libromycin) as well, but not with other cytotoxic drugs such as adriamycin, neocarzinostatin, paraquat, hydrogen peroxide, and N-methyl-N-nitrosourea. The cytotoxicity of BLM and its analogs was potentiated by some polyhydric alcohols as intensely as by glycerol. Polyhydric alcohols containing more than two hydroxyl groups in the molecule were effective in V79 cells, and those containing more than three hydroxyl groups were effective in L1210 cells. The cellular uptake of [3H] peplomycin was not affected by glycerol. For antitumor activity, when 0.5 ml of glycerol (10%) and erythritol (10%) were combined with 2.0 mg/kg/day of BLM, the 5-day treatment of Ehrlich cell-bearing (i.p.) mice prolonged the life span by 244% and 282% (T/C), respectively. When a low dose of BLM (0.2 mg/kg/day) was combined with 0.5 ml of glycerol (20%) and erythritol (30%), the therapeutic gains were 1.82 and 1.88, respectively. These results suggest the possibility that the adjuvant treatment of BLM with polyhydric alcohols might be applied to the clinical treatment of cancerous peritonitis and pleuritis.
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
T
T
Suzuki
K
K
Kohda
Y
Y
Kawazoe
D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000031:analogs & derivatives; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D004357:Drug Synergism; D004896:Erythritol / Q000008:administration & dosage; D005260:Female; D005990:Glycerol / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009374:Neoplasms, Experimental / Q000188:drug therapy; D017663:Peplomycin
D000438:Alcohols; D001761:Bleomycin; D017663:Peplomycin; C054113:liblomycin; D005990:Glycerol; D004896:Erythritol