Immunogenicity of DNA modified by singlet oxygen: implications in systemic lupus erythematosus and cancer

Activation, proliferation and programmed cell death of immune cells are dependent on controlled production of ROS (reactive oxygen species). However, under chronic inflammatory conditions, large amounts of ROS generated are a major cause of many human degenerative diseases. ROS are known to cause DNA damage, leading to strand breaks, base damage and conformational changes. (1)O(2) (singlet oxygen), being one of the most potent ROS, is known to selectively react with the deoxyguanosine moiety in DNA. The effect of (1)O(2), generated by UV irradiation of Methylene Blue, on plasmid DNA was studied by UV spectroscopy and electrophoresis. The antibodies raised against the modified DNA in experimental animals induced a high titre. IgG was purified on a Protein A-Sepharose matrix, and oxidative lesions in DNA of SLE (systemic lupus erythematosus) and cancer patients were probed using anti-((1)O(2)-plasmid DNA) [anti-((1)O(2)-modified plasmid DNA)]. The DNA isolated from the sera of SLE and cancer patients was found to inhibit anti-(1)O(2)-plasmid DNA IgG activity, reiterating the results obtained with serum samples. These binding results indicate the presence of oxidative lesions in the SLE and cancer patients' genome caused by excessive production of ROS. The results confirm the damaging effect ROS has on DNA. The excessive production of reactive oxygen intermediates may be one of the factors responsible for the induction of autoimmune response seen in SLE and cancer.