Bleomycin-dependent damage to the bases in DNA is a minor side reaction.
The antitumor antibiotic bleomycin degrades DNA in the presence of ferric ions and H2O2 or in the presence of ferric ions, oxygen, and ascorbic acid. When DNA degradation is measured as formation of base propenals by the thiobarbituric acid assay, it is not inhibited by superoxide dismutase and scavengers of the hydroxyl radical or by catalase (except that catalase inhibits in the bleomycin/ferric ion/H2O2 system by removing H2O2). Using the technique of gas chromatography/mass spectrometry with selected-ion monitoring, we show that DNA degradation is accompanied by formation of small amounts of modified DNA bases. The products formed are identical with those generated when hydroxyl radicals react with DNA bases. Base modification is significantly inhibited by catalase and partially inhibited by scavengers of the hydroxyl radical and by superoxide dismutase. We suggest that the bleomycin-oxo-iron ion complex that cleaves the DNA to form base propenals can decompose in a minor side reaction to generate hydroxyl radical, which accounts for the base modification in DNA. However, hydroxyl radical makes no detectable contribution to the base propenal formation.
Gajewski
E
E
Center for Chemical Technology, National Institute of Standards and Technology, Gaithersburg, Maryland 20899.
Aruoma
O I
OI
Dizdaroglu
M
M
Halliwell
B
B
D001205:Ascorbic Acid / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D016166:Free Radical Scavengers; D008401:Gas Chromatography-Mass Spectrometry; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D013482:Superoxide Dismutase / Q000494:pharmacology
D016166:Free Radical Scavengers; D001761:Bleomycin; D004247:DNA; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D001205:Ascorbic Acid