Document Detail

DNA alterations induced by the carbon-centered radical derived from the oxidation of 2-phenylethylhydrazine.
MedLine Citation:
PMID:  2539776     Owner:  NLM     Status:  MEDLINE    
The possible significance of carbon-centered radicals in hydrazine-induced carcinogenesis is explored by studies of the interaction between the 2-phenylethyl radical and DNA. The radical is efficiently generated during oxidation of phenelzine (2-phenylethylhydrazine) promoted by oxyhemoglobin or ferricyanide, as demonstrated by spin-trapping experiments and analysis of the reaction products. In the ferricyanide promoted oxidation, ethylbenzene formation accounts for about 40% of the initial drug concentration, from 5 to 100 mM phenelzine. By contrast, product formation in the presence of oxyhemoglobin depends on the enzyme concentration due to the fact that the prosthetic heme is destroyed during catalytic turnover. Covalent binding of the 2-phenylethyl radical to oxyhemoglobin is demonstrated by experiments with 2-[3H]phenelzine, where tritium incorporation to the protein is inhibited by the spin-trap, alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone. The 2-phenylethyl radical is also able to alkylate DNA as suggested by electrophoretic studies with plasmid DNA, and proved by experiments with 2-[3H]-phenelzine. The carbon-centered radical has a preference for attacking guanine residues as demonstrated by the use of sequencing techniques with 32P-DNA probes. The results indicate that the 2-phenylethyl radical is an important product of phenelzine oxidation and that this species can directly damage protein and DNA.
L C Leite; O Augusto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  270     ISSN:  0003-9861     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  1989 May 
Date Detail:
Created Date:  1989-05-24     Completed Date:  1989-05-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  560-72     Citation Subset:  IM    
Department of Biochemistry, Universidade de São Paulo, Brazil.
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MeSH Terms
DNA / metabolism*
DNA Damage*
DNA Probes
Electron Spin Resonance Spectroscopy
Ferricyanides / pharmacology
Free Radicals
Guanine / analysis
Oxygen / metabolism
Oxygen Consumption
Oxyhemoglobins / metabolism*,  pharmacology
Phenelzine / chemical synthesis,  metabolism*
Reg. No./Substance:
0/DNA Probes; 0/Ferricyanides; 0/Free Radicals; 0/Oxyhemoglobins; 13408-62-3/hexacyanoferrate III; 51-71-8/Phenelzine; 73-40-5/Guanine; 7440-44-0/Carbon; 7782-44-7/Oxygen; 9007-49-2/DNA

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