RT Journal Article
SR Electronic
T1 Studies on the interaction of bleomycin A2 with rat lung microsomes. II. Involvement of adventitious iron and reactive oxygen in bleomycin-mediated DNA chain breakage.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 159
OP 165
VO 221
IS 1
A1 M A Trush
A1 E G Mimnaugh
A1 E Ginsburg
A1 T E Gram
YR 1982
UL http://jpet.aspetjournals.org/content/221/1/159.abstract
AB Bleomycin-dependent DNA chain breakage catalyzed by rat lung microsomes and NADPH was significantly inhibited by the reactive oxygen scavengers superoxide dismutase and dimethylurea and by the metal chelator EDTA. Cytochrome c and nitro blue tetrazolium, compounds which interfere with microsomal electron transport, also inhibited bleomycin-mediated DNA chain breakage. In contrast to these agents, ascorbic acid significantly enhanced this bleomycin-mediated reaction. In addition to ascorbic acid, the redox cycling compounds paraquat, nitrofurantoin and mitomycin C also significantly increased the DNA damage by bleomycin. The stimulatory action of these redox cycling compounds was significantly inhibited by superoxide dismutase, demonstrating that reactive oxygen generated by the redox cycling of these compounds was diverted to the bleomycin-DNA complex. These collective observations support the concept that oxidation/reduction of adventitious iron bound by bleomycin and accompanying reactive oxygen generation participate in the microsome-catalyzed DNA damage mediated by bleomycin.