EFFECTS OF IRON, COPPER, COBALT, AND THEIR CHELATORS ON THE CYTO-TOXICITY OF BLEOMYCIN

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (3) , 1049-1053
Abstract
Bleomycin widely used for treating several types of tumors. The effect of iron, copper, cobalt, and their chelators on bleomycin cytotoxicity were tested using Chinese hamster V79 cells. The results suggest that chelating bleomycin with copper or adding an iron chelator (deferoxamine), diethylenetriamine pentaacetic acid, and a copper chelator (penicillamine) shows no effect on bleomycin cytotoxicity. Iron dextran and a metal chelator, diethyldithiocarbamate (DDC), with bleomycin show enhanced cytotoxicity. Cobalt-chelated bleomycin is not cytotoxic but is cytotoxic when combined with DDC. Different mechanisms may be contributing to the enhanced toxicity of bleomycin with iron dextran and DDC. Bleomycin acts as a ferrous oxidase which promotes the iron toxicity. In the case of DDC, it can act as a reducing agent or it can help to maintain the bleomycin:metal complex in the reduced form which can generate radicals.