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

Biochemistry
L R SolomonP L Moseley

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-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-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 10(6) molar excess of EDTA over bleomycin. Furthermore, we found that the half-life for inactivation of bleomycin-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-Fe with DNA.

References

Oct 1, 1977·Nucleic Acids Research·L F PovirkF Hutchinson
Jul 11, 1978·Biochemistry·E A SausvilleS B Horwitz
Jun 1, 1979·Annals of Internal Medicine·J M Bennett, S D Reich
Sep 1, 1987·The Journal of Antibiotics·J AronovitchG Czapski
Jan 1, 1985·The Journal of Clinical Investigation·S WeberT A Raffin
Jun 14, 1967·Journal of Molecular Biology·B Hirt

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Citations

Oct 13, 1992·Biochemistry·G R Buettner, P L Moseley
Sep 24, 2002·The Journal of Biological Chemistry·Shisheng Li, Michael J Smerdon

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