Title

Selenium Compounds and their Effects on Oxidative DNA Damage

Authors

William E. Hart, Rose-Hulman Institute of Technology
Steven P. Marczak, University of Notre Dame
Andrew R. Kneller, Indiana University - Bloomington
Robert A. French, Rose-Hulman Institute of TechnologyFollow
Daniel L. Morris Jr., Rose-Hulman Institute of TechnologyFollow

Document Type

Article

Publication Date

3-6-2013

First Advisor

Dan Morris

Abstract

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 ionicmechanism, and this type of damage also decreases significantly when the selenium compounds are allowed to interact with themetal ions before adding DNA. Fluorescence studies using dihydrodichlorofluorescein diacetate (DCF-DA) to probe ROS formation indicate that the majority of the SeO₂- and SeO₃^2- - metal systems in combination with H2O2 (no DNA present) produce ROS to the same degree as themetal/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.

Comments

RHURP 13-02

Recommended Citation

Hart, William E.; Marczak, Steven P.; Kneller, Andrew R.; French, Robert A.; and Morris, Daniel L. Jr., "Selenium Compounds and their Effects on Oxidative DNA Damage" (2013). Rose-Hulman Undergraduate Research Publications. 5.
https://scholar.rose-hulman.edu/undergrad_research_pubs/5