Inhibition of the lethality of bleomycin A5 in L-cells by hirudonine.
The lethality of several individual bleomycin derivatives, i.e., the spermidine derivative (A5), The dimethyl sulfonium aminopropyl derivative (A2), and the agmatine derivative (B2), was compared on mouse fibroblasts. The spermidine derivative, bleomycin A5, was the most toxic, producing more than a 2-log drop in clonability in 50 hr at 20 microng/ml. 6-Azauridine, a relatively nonlethal inhibitor of RNA synthesis and cell multiplication, produced a 60% decrease of adenine incorporation into nucleic acids without inhibiting the lethal action of A5. This result differed from the effects of inhibition of RNA synthesis on the lethality of A5 in Escherichia coli. Hirudonine (1,8-diamidino-spermidine) markedly and specifically inhibited the lethal effects of A5 in L-cells but not in E. coli. However, hirudonine did not affect the toxicity of A2 and B2, separately or together, as it did in the mixture used clinically. Nor did arcaine (diamindinoputrescine) reduce the lethality of the agmatine (monoamidinoputrescine) derivative, B2.
D000578:Amidines / Q000494:pharmacology; D001380:Azauridine / Q000494:pharmacology; D001761:Bleomycin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D007739:L Cells; D012313:RNA / Q000096:biosynthesis; D013095:Spermidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000578:Amidines; D001761:Bleomycin; C014590:hirudonine; D012313:RNA; D001380:Azauridine; D013095:Spermidine