Activity of bleomycin in iron- and copper-deficient cells.
Three models were used to examine the requirement of bleomycin (Blm) for iron (Fe) to carry out its antitumor or cytotoxic activity. Mice were made iron deficient by dietary means. Animals with depressed iron stores in liver and low plasma and ascites fluid iron supported Ehrlich tumor growth as well as mice maintained on a control diet. Bleomycin was equally effective against this tumor in iron-deficient mice as it was against the tumor in iron-sufficient controls. Likewise, nutrient copper deficiency did not change the efficacy of the drug. Ehrlich cells in culture were treated with a non-growth inhibiting concentration of the chelating agent, 1,10-phenanthroline before or during their exposure to bleomycin. Again, the treated cells were as sensitive to drug as controls, despite the fact that this ligand reduces cellular iron and zinc and can extract iron from Fe(II)Blm. Lastly, it was demonstrated that iron-depleted Euglena gracilis cells growing at reduced rates were as sensitive to growth inhibition by bleomycin as control cells.
Lyman
S
S
Department of Chemistry, University of Wisconsin-Milwaukee 53201.
Taylor
P
P
Lornitzo
F
F
Wier
A
A
Stone
D
D
Antholine
W E
WE
Petering
D H
DH
D000818:Animals; D001201:Ascites / Q000378:metabolism; D001761:Bleomycin / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003300:Copper / Q000008:administration & dosage / Q000172:deficiency*; D004032:Diet; D005056:Euglena gracilis / Q000187:drug effects; D005260:Female; D007501:Iron / Q000008:administration & dosage; D007502:Iron Chelating Agents / Q000494:pharmacology; D000090463:Iron Deficiencies; D051379:Mice; D010618:Phenanthrolines / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007502:Iron Chelating Agents; D010618:Phenanthrolines; D001761:Bleomycin; D003300:Copper; D007501:Iron; C025205:1,10-phenanthroline