Document Detail


Bleomycin may be activated for DNA cleavage by NADPH-cytochrome P-450 reductase.
MedLine Citation:
PMID:  6084519     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
R E Kilkuskie; T L Macdonald; S M Hecht
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemistry     Volume:  23     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  1984 Dec 
Date Detail:
Created Date:  1985-04-18     Completed Date:  1985-04-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  6165-71     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Bleomycin / 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:
CA-29235/CA/NCI NIH HHS; ES-03181/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
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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