ja991574a_si_001.pdf (149.42 kB)
Chemistry of the Bleomycin-Induced Alkali-Labile DNA Lesion
journal contribution
posted on 1999-09-16, 00:00 authored by Mariko Aso, Mitsumasa Kondo, Hiroshi Suemune, Sidney M. HechtTreatment of B-form DNA with the antitumor antibiotic bleomycin in the presence of Fe2+ and O2
affords both DNA strand scission and the formation of alkali-labile lesions, the proportion of which is quite
sensitive to the concentration of O2 present. The alkali-labile lesions can undergo fragmentation cleanly in the
presence of n-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 n-BuNH2, as well as the identification of the byproduct of the fragmentation reaction containing
the carbon atoms originally present within the alkali-labile lesion.