Light-induced nicking of deoxyribonucleic acid by cobalt(III) bleomycins

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Abstract
The anticancer drug bleomycin is a glycopeptide that causes strand scission of DNA both in vivo and in vitro. Cleavage of DNA by bleomycin has been studied extensively in vitro, with the findings that Fe2+ and O2 must be present and that addition of reducing agents greatly enhances the reaction. To date, only Fe has been shown to be an effective metal cofactor for the cleavage of DNA by bleomycin. Two stable Co(III) complexes of bleomycin are strikingly effective in causing single-strand breaks (nicks) in supercoiled DNA in the presence of UV or visible radiation. For example, 366-nm light from an 18-W long-wavelength mercury lamp for 1 h causes 10-6 M Co(III) bleomycin to completely convert supercoiled .vphi.X174 DNA (10-8 M DNA, 10-4 M phosphate) into the nicked circular form. Numerous alkali-labile sites are produced on the DNA during this treatment. The observed reactions are not caused by adventitious Fe, and they occur only in the presence of Co(III) bleomycin and light.