<p> Hydrogen sulfide (H<sub>2</sub>S) is more commonly known for its toxic properties; however, recently, there has been evidence that this small, gaseous molecule could serve as an endogenous cell-signaling agent. Surprisingly, a number of studies have also provided evidence that H<sub> 2</sub>S is a DNA-damaging mutagen. Using a plasmid-based DNA strand cleavage assay, we examined the chemical mechanisms of DNA damage by H<sub>2</sub>S. We found single-strand DNA cleavage was caused by micromolar concentrations of H<sub>2</sub>S. The mechanistic process was studied and was shown to involve the autoxidation of H<sub>2</sub>S to generate superoxide, hydrogen peroxide, and ultimately hydroxyl radical, a well-known DNA-damaging agent, via a trace metal-mediated Fenton-type reaction. In the presence of physiological thiol concentrations, DNA strand cleavage by H<sub>2</sub>S still occurred. The oxidation byproducts of H<sub>2</sub>S, such as thiosulfate, sulfite, and sulfate, do not contribute to DNA strand cleavage. However, the initially generated oxidation products, like persulfide (S<sub>2</sub><sup>2-</sup>), most likely go through rapid autoxidation reactions, which contribute to superoxide generation. This autoxidation process is of potential relevance to both the genotoxic and cell signaling properties of H<sub>2</sub>S.</p>
| Identifer | oai:union.ndltd.org:PROQUEST/oai:pqdtoai.proquest.com:10180877 |
| Date | 18 November 2016 |
| Creators | Hoffman, Marjorie A. |
| Publisher | University of Missouri - Columbia |
| Source Sets | ProQuest.com |
| Language | English |
| Detected Language | English |
| Type | thesis |
Page generated in 0.0019 seconds