Cytotoxic and antitumor properties of bleomycin and several of its metal complexes

Abstract

The concentration-dependent cytotoxicity and antitumor activity of bleomycin (Blm) and Cu-, Zn-, Fe(III)- and CoBlm were examined using [mouse] Ehrlich cells in culture and the Ehrlich ascites tumor. The order of activity in culture under several conditions is CuBlm .apprxeq. Blm .apprxeq. ZnBlm > Fe(III)Blm .mchgt. CoBlm .apprxeq. control. Short exposures of cells to drugs in the presence or absence of serum produced effects on cell proliferation similar to 48 h incubations. With Blm and CuBlm there was no obvious relationship between cytotoxicity and the modest short-term inhibition of DNA synthesis by the drugs. The antitumor experiments produced qualitatively similar results with the order of antitumor potency being CuBlm > Blm > ZnBlm .apprxeq. FeBlm .mchgt. CoBlm .apprxeq. control tumor. The host toxicity produced by these drugs as measured by weight loss had the opposite ordering: CoBlm .mchlt. FeBlm .mchlt. ZnBlm < Blm < CuBlm. At therapeutically effective concentrations, FeBlm was significantly less toxic relative to the other active agents.