Free radical metabolism of hydralazine. Binding and degradation of nucleic acids.

The binding of hydralazine, a hydrazine-containing hypotensive drug, to nucleic acids has been studied. Binding of this drug to biopolymers was assayed using spin-trapping techniques in the presence of various metal ions, which produce free radical intermediates from hydralazine [B. K. Sinha and A. G. Motten, Biochem, biophys. Res. Commun. 105, 1044 (1982)]. Some interaction was detected with the single-stranded nucleic acids. Hydralazine binds strongly to the native DNA, most likely by intercalation of the drug into DNA bases. In the presence of nucleic acids and metal ions, hydralazine stimulated the production of OH(.) radicals which was inversely proportional to the degree of binding. Aldehyde formation in DNA was also induced by hydralazine which was stimulated by superoxide dismutase and inhibited by catalase.