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Increased Sensitivity of PBMCs Isolated from Patients with Rheumatoid Arthritis to DNA Damaging Agents Is Connected with Inefficient DNA Repair

1
Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
2
Department of Rheumatology, Medical University of Lodz, 92-115 Lodz, Poland
3
Biobank, Department of Immunology and Allergy, Medical University of Lodz, 92-213 Lodz, Poland
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(4), 988; https://doi.org/10.3390/jcm9040988
Received: 4 March 2020 / Revised: 23 March 2020 / Accepted: 29 March 2020 / Published: 1 April 2020
(This article belongs to the Section Immunology)
Rheumatoid arthritis (RA) is a systemic, inflammatory disease of the joints and surrounding tissues. RA manifests itself with severe joint pain, articular inflammation, and oxidative stress. RA is associated with certain types of cancer. We have assumed that RA patients’ increased susceptibility to cancer may be linked with genomic instability induced by impaired DNA repair and sensitivity to DNA damaging agents. The aim of this work was to analyze the sensitivity of peripheral blood mononuclear cells (PBMCs) isolated from RA patients to DNA damaging agents: tert-butyl hydroperoxide (TBH), bleomycin, ultraviolet (UV) radiation, and methyl methanesulfonate (MMS) and calculate the repair efficiency. TBH induce oxidative DNA lesions repaired mainly by base excision repair (BER). Bleomycin induced mainly DNA double-strand breaks repaired by non-homologous end joining (NHEJ) and homologous recombination repair (HRR). We included 20 rheumatoid arthritis patients and 20 healthy controls and used an alkaline version of the comet assay with modification to measure sensitivity to DNA damaging agents and DNA repair efficiency. We found an increased number of DNA breaks and alkali-labile sites in the RA patients compared to those in the controls. Exposure to DNA damaging agents evoked the same increased damage in both groups, but we observed statistically higher PMBC sensitivity to TBH, MMS, bleomycin as well as UV. Examination of the repair kinetics of both groups revealed that the DNA lesions induced by TBH and bleomycin were more efficiently repaired in the controls than in the patients. These data suggest impaired DNA repair in RA patients, which may accelerate PBMC aging and/or lead to higher cancer incidence among RA patients. View Full-Text
Keywords: DNA damage and repair; rheumatoid arthritis; oxidative DNA lesions; DNA double-strand breaks; comet assay DNA damage and repair; rheumatoid arthritis; oxidative DNA lesions; DNA double-strand breaks; comet assay
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MDPI and ACS Style

Galita, G.; Brzezińska, O.; Gulbas, I.; Sarnik, J.; Poplawska, M.; Makowska, J.; Poplawski, T. Increased Sensitivity of PBMCs Isolated from Patients with Rheumatoid Arthritis to DNA Damaging Agents Is Connected with Inefficient DNA Repair. J. Clin. Med. 2020, 9, 988. https://doi.org/10.3390/jcm9040988

AMA Style

Galita G, Brzezińska O, Gulbas I, Sarnik J, Poplawska M, Makowska J, Poplawski T. Increased Sensitivity of PBMCs Isolated from Patients with Rheumatoid Arthritis to DNA Damaging Agents Is Connected with Inefficient DNA Repair. Journal of Clinical Medicine. 2020; 9(4):988. https://doi.org/10.3390/jcm9040988

Chicago/Turabian Style

Galita, Grzegorz, Olga Brzezińska, Izabela Gulbas, Joanna Sarnik, Marta Poplawska, Joanna Makowska, and Tomasz Poplawski. 2020. "Increased Sensitivity of PBMCs Isolated from Patients with Rheumatoid Arthritis to DNA Damaging Agents Is Connected with Inefficient DNA Repair" Journal of Clinical Medicine 9, no. 4: 988. https://doi.org/10.3390/jcm9040988

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