Genetic and epigenetic effects of oxidative stress: a role in disease.
Both endogenous and exogenous processes generate free radicals and reactive oxygen species. If this production overwhelms the cell’s antioxidant defences, this leads to oxidative stress. Oxidative stress has an important role in numerous pathological conditions, including cancer, cardiovascular, respiratory and neurological disease via its detrimental effects upon cellular function. This includes mutation, altered gene expression, acceleration of telomere shortening and the promotion of microsatellite instability. Damage to DNA is receiving most attention, due to the significant effects upon cell function, plus clear mechanistic relevance to the disease process.
The aim of my research is to better understand how oxidative stress alters cellular function, and how this then leads to disease. This is achieved by a combination of molecular biology techniques, and biochemical analyses applied to both cell culture, and studies in humans.
A better understanding of how oxidative stress influences disease, will allow us develop intervention strategies, plus the development of biomarkers of oxidative stress may have predictive and prognostic properties.
Cooke, MS., Evans, MD., Dizdaroglu, M. and Lunec, J. (2003) Oxidative DNA damage: mechanisms, mutation and disease. FASEB J., 17, 1195-1214.
Evans, MD. and Cooke, MS. (2004) Factors contributing to the outcome of oxidative damage to nucleic acids. Bioessays. 26, #5, 533-542.
Evans, MD., Saparbaev, M. and Cooke, MS. (2010) DNA repair and the origins of urinary oxidised 2'-deoxyribonucleosides. Mutagenesis 25, 433-442.
Al-Salmani, K. et al. (2011) Evaluation of storage and DNA damage analysis of whole blood by Comet assay. Free Radic. Biol. Med., 51, 719-725.
Barregard, L. et al. (2013) Human and methodological sources of variability in the measurement of urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine. Antioxidants and Redox Signalling 18, 2377-2391.