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© 1984 Oxford University Press

other

DNA strand scission by the carbon radical derived from 2-phenyl-ethylhydrazine metabolism

Ohara Augusto, Adelaide Faljoni-Alário, Luciana C. C. Leite and Francisco G. Nóbrega

Department of Biochemistry, Instituto de Química, Universidade de Sao Paulo Caixa Postal 20780, 01498-Sao Paulo, S.P., Brazil

Oxyhemoglobin catalyzed oxidation of the tranquilizing drug 2-phenylethylhydrazine induces single strand breaks (nicks) in the supercoiled pBR322 plasmid DNA. Spin-trapping studies have established a clear correlation between 2-phenylethyl radical yield and the DNA strand scission activity observed during 2-phenylethylhydrazine oxidation. The same correlation is obtained in the presence of active oxygen species scavengers or when the carbon radical is generated under anaerobic conditions by ferricyanide oxidation of the drug. In addition to DNA damage, the 2-phenylethylhydrazine turnover by oxyhemoglobin promotes destruction of the hemo-protein catalyst to as yet unidentified products. These results may be relevant for the expression of the mutagenic and carcinogenic properties of hydrazine derivatives.


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Home page
 Toxicol PatholHome page
A. Tomasi, E. Albano, B. Botti, and V. Vannini
Detection of Free Radical Intermediates in the Oxidative Metabolism of Carcinogenic Hydrazine Derivatives
Toxicol Pathol, February 1, 1987; 15(2): 178 - 183.
[Abstract] [PDF]


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