The abilities of selenium dioxide and selenite ion to coordinate DNA-bound metal ions and decrease oxidative DNA damage

Several transition metals react with H2O2 and produce reactive oxygen species (ROS) responsible for oxidative damage linked to many diseases and disorders, and species that form coordination complexes with these metal ions show promise as antioxidants. The present study demonstrates that metal-mediated radical and non-radical oxidative DNA damage decreases when selenium dioxide (SeO2) and sodium selenite (Na2SeO3) are present. Radical-induced damage is associated with production of 8-hydroxy-2′-deoxyguanosine (8-OH-dG), which arises from ROS generated at or near the guanine base, and the selenium compounds reduce Fe(II)-, Cr(III)- and Cu(II)-mediated radical damage to differing degrees based on the identity of the metal ion and the order in which the metals, selenium compounds and DNA are combined. Radical damage arising from Fe(II) and Cr(III) decreases substantially when they are pre-incubated with the selenium compounds prior to adding DNA. Non-radical damage is associated with oxidation of the adenine base in the presence of high H2O2 concentrations through an ionic mechanism, and this type of damage also decreases significantly when the selenium compounds are allowed to interact with the metal ions before adding DNA. Fluorescence studies using dihydrodichlorofluorescein diacetate (DCF-DA) to probe ROS formation indicate that the majority of the SeO2- and SeO32−-metal systems in combination with H2O2 (no DNA present) produce ROS to the same degree as the metal/H2O2 systems in the absence of the selenium compounds, suggesting that selenium–metal complexes react with H2O2 in a sacrificial manner that protects DNA from oxidative damage. SeO2 and SeO32− decrease radical-induced production of 8-hydroxy-2′-deoxyguanosine (8-OH-dG) and non-radical induced production of 2′-deoxyadenosine N-1 oxide (dA N-1 oxide). [Display omitted] •Selenium dioxide and selenite ion decrease metal ion mediated DNA oxidation.•They form stable complexes with Fe(II), Cr(III) and Cu(II).•They do not complex DNA-bound metal ions as effectively as those free in solution.•The metal–selenium complexes react with H2O2.