| Bleomycin may be activated for DNA cleavage by NADPH-cytochrome P-450 reductase. | |
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MedLine Citation:
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PMID: 6084519 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the presence of NADPH and O2, NADPH-cytochrome P-450 reductase was found to activate Fe(III)-bleomycin A2 for DNA strand scission. Consistent with observations made previously when cccDNA was incubated in the presence of bleomycin and Fe(II) + O2 or Fe(III) + C6H5IO, degradation of DNA by NADPH-cytochrome P-450 reductase activated Fe(III)-bleomycin A2 produced both single- and double-strand nicks with concomitant formation of malondialdehyde (precursors). Cu(II)-bleomycin A2 also produced nicks in SV40 DNA following activation with NADPH-cytochrome P-450 reductase, but these were not accompanied by the formation of malondialdehyde (precursors). These findings confirm the activity of copper bleomycin in DNA strand scission and indicate that it degrades DNA in a fashion that differs mechanistically from that of iron bleomycin. The present findings also-establish the most facile pathways for enzymatic activation of Fe(III)-bleomycin and Cu(II)-bleomycin, provide data concerning the nature of the activated metallobleomycins, and extend the analogy between the chemistry of cytochrome P-450 and bleomycin. |
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Authors:
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R E Kilkuskie; T L Macdonald; S M Hecht |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Biochemistry Volume: 23 ISSN: 0006-2960 ISO Abbreviation: Biochemistry Publication Date: 1984 Dec |
Date Detail:
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Created Date: 1985-04-18 Completed Date: 1985-04-18 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 6165-71 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Bleomycin
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metabolism* Copper / pharmacology DNA / metabolism* DNA, Superhelical / metabolism DNA, Viral / metabolism Ferric Compounds / pharmacology Kinetics NADPH-Ferrihemoprotein Reductase / pharmacology* Oxygen / pharmacology Simian virus 40 / genetics |
| Grant Support | |
ID/Acronym/Agency:
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CA-29235/CA/NCI NIH HHS; ES-03181/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Superhelical; 0/DNA, Viral; 0/Ferric Compounds; 0/copper bleomycin; 11056-06-7/Bleomycin; 7440-50-8/Copper; 7782-44-7/Oxygen; 9007-49-2/DNA; EC 1.6.2.4/NADPH-Ferrihemoprotein Reductase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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