Studies on the interaction of bleomycin A2 with rat lung microsomes. II. Involvement of adventitious iron and reactive oxyggen in bleomycin-mediated DNA chain breakage

M. A. Trush, E. G. Mimnaugh, E. Ginsburg, T. E. Gram

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)159-165
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume221
Issue number1
StatePublished - 1982
Externally publishedYes

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Bleomycin
Microsomes
Iron
Lung
Oxidation-Reduction
DNA
Oxygen
Ascorbic Acid
DNA Damage
Superoxide Dismutase
Nitrofurantoin
Paraquat
Mitomycin
Chelating Agents
Electron Transport
Cytochromes c
NADP
Edetic Acid
Contrast Media
indium-bleomycin

ASJC Scopus subject areas

  • Pharmacology

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Studies on the interaction of bleomycin A2 with rat lung microsomes. II. Involvement of adventitious iron and reactive oxyggen in bleomycin-mediated DNA chain breakage. / Trush, M. A.; Mimnaugh, E. G.; Ginsburg, E.; Gram, T. E.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 221, No. 1, 1982, p. 159-165.

Research output: Contribution to journalArticle

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