Site-specific DNA damage induced by NADH in the presence of copper(II): role of active oxygen species

The mechanism behind the site-specific DNA damage by NADPH with copper(II) was evaluated by DNA sequencing analysis, which utilized the 32P 5' end-labeled DNA fragments prepared from human p53 tumor inhibitor. Indeed, NADH and other endogenous reductants bring on DNA damage in the presence of Cu(II), with the inducing effect order of ascorbate > GSH > NADH > NADPH. Spectroscopic results suggest the production of a high redox potential copper from DNA/metal ion, which oxidizes NADH, and the reaction of H2O2 with Cu(I) which gives active oxygen species responsible for DNA damage.