Manganese-mediated oxidative damage of cellular and isolated DNA by isoniazid and related hydrazines: non-Fenton-type hydroxyl radical formation.

摘要: The mechanism by which hydrazines induce damage to cellular and isolated DNA in the presence of metal ions has been investigated pulsed-field gel electrophoresis (PFGE), sequencing methods, ESR spin-trapping technique. For detection single-strand breaks PFGE, an experimental procedure with alkali treatment designed. Isoniazid, hydrazine, phenylhydrazine induced single- double-strand cells pretreated Mn(II), whereas iproniazid did not. With 32P-DNA, isoniazid produced Cu(II), or Mn(III). Iproniazid only Cu(II). Cu(II)-mediated is due active oxygen species other than hydroxyl free radical (.OH), presumably Cu(I)-peroxide complex. Cleavage plus Mn(II) occurred without marked site specificity. was inhibited .OH scavengers superoxide dismutase (SOD) but not catalase, suggesting involvement formed via O2- H2O2. Consistently, experiments formation observed during Mn(II)-catalyzed autoxidation isoniazid, SOD, catalase. no little .OH. We propose a reaction for H2O2 intermediate manganese-catalyzed hydrazine. present previous data raise possibility that Mn(II)-induced may occur, at least part, through non-Fenton-type reaction.