Chemistry of the Bleomycin-Induced Alkali-Labile DNA Lesion

Treatment of B-form DNA with the antitumor antibiotic bleomycin in the presence of Fe<sup>2+</sup> and O<sub>2</sub> affords both DNA strand scission and the formation of alkali-labile lesions, the proportion of which is quite sensitive to the concentration of O<sub>2</sub> present. The alkali-labile lesions can undergo fragmentation cleanly in the presence of <i>n</i>-butylamine to afford DNA fragments containing 5‘- and 3‘-phosphate termini at the site of the alkali-labile lesion. The mechanism of decomposition of the alkali-labile lesion was studied, leading to identification of a putative intermediate that is converted readily to an (oligo)nucleotide 3‘-phosphate in the presence of <i>n</i>-BuNH<sub>2</sub>, as well as the identification of the byproduct of the fragmentation reaction containing the carbon atoms originally present within the alkali-labile lesion.