Exercise-Induced DNA Damage
: Effects of Hypoxia and Antioxidant Intervention

Student thesis: Doctoral Thesis

Abstract

Abstract
Reactive oxygen and nitrogen species (RONS) are continuously produced within the body during oxidative metabolism, and through normal immune function. When contained within a homeostatic balance, these molecules are part of a normal physiological function, and play integral signalling roles in cell growth, proliferation, and differentiation. This equilibrium is tightly regulated by a range of enzymatic and non-enzymatic antioxidants which seek to prevent detrimental reactions to biologically important macromolecules. The purpose of this thesis was twofold. Firstly, the use of various high-intensity exercise protocols was employed to investigate the effect on oxidative stress within circulating peripheral blood mononuclear cells and skeletal muscle tissue with a particular emphasis on DNA damage. Additionally, an environmental stressor was used via normobaric hypoxia to comprehensively elucidate the cell DNA damage-repair response, alongside systemic measures of oxidative stress following constant-load high-intensity exercise. Secondly, this thesis aimed to examine the efficacy of novel antioxidant supplementation on measures of exercise-induced oxidative stress; specifically, a plant-based combination of barley- and wheat-grass juice, and the mitochondrial-targeted antioxidant, Mitoquinone. Across all studies, it was confirmed that exercise of sufficient intensity (regardless of duration) provided a challenging physiological stress capable of inducing oxidative damage to DNA and lipids; likely through the generation of RONS, and concurrent reduction in antioxidant capacity. Furthermore, it was determined that peripheral blood mononuclear cells have an efficient and effective DNA damage-repair response, with maximal repair occurring within 24-hours for both single- and double-strand DNA damage; this response was marginally exacerbated in the hypoxic condition. The aforementioned modifications to DNA as a function of exercise, were concurrently aligned with systemic biomarkers of oxidative stress; including but not limited to, lipid peroxidation, lipid soluble antioxidants, and the ascorbyl free radical. With regards to plant-based antioxidant supplementation, although there was no meaningful prophylactic effect on a statistical level, a combination of barley- and wheat-grass juice did appear to provide a marginal protective effect against exercise-induced oxidative stress. On a more molecular level, mitochondrial-targeted supplementation for 21-days abrogated oxidative damage to the mitochondrial genome following high-intensity intermittent exercise; likely, through the scavenging of exercise-induced RONS, and/or secondary oxidation products of mitochondrial lipid peroxidation. The results of the studies demonstrate an increase in oxidative stress following high-intensity exercise as evidenced by an increase in DNA damage (single-strand breaks, double-strand breaks, base oxidation) across nuclear and mitochondrial genomes, and changes to other systemic measures, such as: lipid hydroperoxides, lipid soluble antioxidants, and the ascorbyl free radical. The DNA damage-repair response was exacerbated by normobaric hypoxia with single- and double-strand DNA damage returning to baseline by 48-hours and 24-hours respectively. Finally, the data also indicates a potential prophylactic effect by supplementing with a plant-based nutraceutical, and mitochondrial-targeted antioxidant; however, further research is warranted to elucidate the underlying biochemical processes.

Date of AwardMay 2020
Original languageEnglish
SupervisorCiara Hughes (Supervisor) & Gareth Davison (Supervisor)

Keywords

  • Oxidative Stress
  • Comet Assay
  • Redox Biology

Cite this

Exercise-Induced DNA Damage: Effects of Hypoxia and Antioxidant Intervention
Williamson, J. (Author). May 2020

Student thesis: Doctoral Thesis