PMID: 2539776May 1, 1989

DNA alterations induced by the carbon-centered radical derived from the oxidation of 2-phenylethylhydrazine

Archives of Biochemistry and Biophysics
L C Leite, O Augusto

Abstract

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 tec...Continue Reading

References

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Citations

Sep 1, 1993·Free Radical Biology & Medicine·O Augusto
Mar 4, 2005·Biological & Pharmaceutical Bulletin·Nobuhiro KashigeTadatoshi Yamaguchi
Apr 6, 2007·Chemical & Pharmaceutical Bulletin·Tadatoshi YamaguchiKazunobu Harano

Related Concepts

Ferricyanide
Alkylation
Vitreous Carbon
DNA, Double-Stranded
Genotoxic Stress
Electron Spin Resonance Spectroscopy
Ferricyanides
Free Radicals
Guanine
Oxidation-Reduction

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