Dissertation/Thesis Abstract

Generation of DNA-damaging reactive oxygen species via the autoxidation of hydrogen sulfide under physiologically relevant conditions
by Hoffman, Marjorie A., M.S., University of Missouri - Columbia, 2014, 46; 10180877
Abstract (Summary)

Hydrogen sulfide (H2S) 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 2S is a DNA-damaging mutagen. Using a plasmid-based DNA strand cleavage assay, we examined the chemical mechanisms of DNA damage by H2S. We found single-strand DNA cleavage was caused by micromolar concentrations of H2S. The mechanistic process was studied and was shown to involve the autoxidation of H2S 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 H2S still occurred. The oxidation byproducts of H2S, such as thiosulfate, sulfite, and sulfate, do not contribute to DNA strand cleavage. However, the initially generated oxidation products, like persulfide (S22-), 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 H2S.

Indexing (document details)
Advisor: Gates, Kent S.
Commitee:
School: University of Missouri - Columbia
School Location: United States -- Missouri
Source: MAI 56/01M(E), Masters Abstracts International
Source Type: DISSERTATION
Subjects: Toxicology, Surgery, Chemistry, Biochemistry
Keywords: Autoxidation, DNA-damage, Hydrogen sulfide, Reactive oxygen species
Publication Number: 10180877
ISBN: 9781369295436
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