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

Abstract

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.