Elevated Level of DNA Damage and Impaired Repair of DNA Oxidative Damage in Multiple Sclerosis Patients
Beata Filipek1, Tomasz Poplawski2
1International Doctoral School Medical University of Lodz, 2Department of Pharmaceutical Microbiology and Biochemistry, Medical University of Lodz
Objective:
The aim of this work was to analyze the sensitivity of peripheral blood mononuclear cells (PBMC) isolated from MS patients to DNA damaging agents inducing oxidative DNA lesions - tert-butyl hydroperoxide (TBH) and calculate the repair efficiency.
Background:
Multiple sclerosis (MS) is a common neurodegenerative disease in which axon demyelination and nerve cell death follow the inflammatory process. The etiology of MS still remains unclear. We assumed that MS pathogenesis includes damage to cell DNA caused by oxidative stress. The further fate of the cells depends on the effectiveness of DNA repair.
Design/Methods:
We included 30 multiple sclerosis patients ( median age=39, SD=12,05; 23F, 7M) and 30 healthy controls. We used an alkaline version of the comet assay (single-cell gel electrophoresis) with modifications to measure sensitivity to DNA damaging agents and repair efficiency.
Results:
We found an increased number of oxidative DNA lesions in the MS patients as compared to the controls. Exposure to TBH evoked similar increased damage in both groups, but we observed statistically higher PMBC sensitivity to TBH (MS-25.3 vs 10.6 in control). Examination of the repair kinetics of both groups revealed that the DNA lesions induced by TBH were more efficiently repaired in the controls than in the patients (ROC area curve 0.69; p<0.05 for TBH).
Conclusions:
These preliminary data suggest impaired repair of oxidative DNA lesions in MS patients. The level of DNA oxidative damage and diminished repair efficiency in patients’ blood cells may be considered potential biomarkers of multiple sclerosis. Further investigations are needed to understand the role of DNA damage and repair in MS pathogenesis.