To study this we have investigated one form of DNA damage by measuring strand breaks in peripheral blood mononuclear cells from patients with rheumatoid arthritis
2008
Key concepts
Scholarcy highlights
- Immune dysfunction is linked with lymphocyte DNA metabolism
- Mononuclear cells from patients with rheumatoid arthritis showed an increased rate of DNA unwinding compared with control subjects
- DNA can be damaged by many agents such as drugs, radiation, free radicals, and enzymes.'0 Various forms of chemical damage have been described, including the disruption of phosphodiester bonds producing single and double strand breaks, the formation of DNA-DNA and DNA-protein crosslinks, and base modifications." DNA is never perfect, as all types of damage can be observed in freshly isolated
- We have investigated DNA integrity in diseased and normal mononuclear cells using an accurate and sensitive DNA unwinding assay
- Our results indicate that DNA strand breaks are significantly more common in mononuclear cells from patients with RA than in cells from the other groups studied
- In isolated DNA most generating systems for oxygen free radicals cause DNA strand breaks.' As there is an increased production of oxygen free radicals in patients with inflammatory diseases, such as RA," these mechanisms may be of relevance
- This evidence, together with our more quantitative data for damaged DNA in patients with rheumatoid arthritis, indicates a lack of effective repair of DNA lesions such as strand scission and suggests a mechanism for autoimmune pathogenesis. Our findings in patients with RA could represent either general cleavage of mononuclear cell DNA or damage to DNA in a particular type or subset of cell
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