Bleomycin.cntdot.iron can degrade DNA in the presence of excess ethylenediaminetetraacetic acid in vitro

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Abstract
The antineoplastic drug bleomycin, when complexed to Fe(II), causes both single- and double-stranded lesions in DNA in vitro. EDTA is commonly used to inhibit the reaction of bleomycin.cntdot.Fe with DNA, presumably by removing the metal cofactor. In this study, we utilized a simple assay involving the conversion of supercoiled plasmid DNA to the nicked or linear forms to further investigate the ability of bleomycin.cntdot.Fe to degrade DNA in the presence of EDTA. We found that a 1:1 complex of bleomycin and Fe can degrade plasmid DNA even in the presence of a 106 molar excess of EDTA over bleomycin. Furthermore, we found that the half-life for inactivation of bleomycin.cntdot.Fe by excess EDTA is about 1.5 h. Finally, we demonstrate that excess bleomycin associated with the outer plasma membranes of cells can damage DNA after the cells are lysed in buffers containing EDTA and SDS. These results suggest that EDTA may not be an efficient inhibitor of the reaction of bleomycin.cntdot.Fe with DNA.