INHIBITION OF LETHALITY OF BLEOMYCIN-A5 IN L-CELLS BY HIRUDONINE

  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (5) , 1384-1388
Abstract
The lethality of several antitumor bleomycin derivatives, i.e, the spermidine derivative (A5), the dimethyl sulfonium aminopropyl derivative (A2) and the agmatine derivative (B2), was compared in mouse fibroblasts. The spermidine derivative, bleomycin A5, was the most toxic, producing more than a 2 log drop in clonability in 50 h at 20 .mu.g/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. Hiudonine (1,8-diamidinospermidine) markedly and specifically inhibited the lethal effects of A5 in L-cells but not in E. coli. Hirudonine did not affect the toxicity of A2 and B2, separately or together, as it did in the mixture used clinically. Nor did arcaine (diamidinoputrescine) reduce the lethality of the agmatine (monoamidinoputrescine) derivative, B2.

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