Role of ROS modified human DNA in the pathogenesis and etiology of cancer

The effect of hydroxyl radical, generated by ultraviolet (UV) irradiation o f hydrogen peroxide, on human placental DNA was monitored by UV spectroscop y, melting temperature studies, S-1 nuclease digestibility and hydroxyapati te column chromatography. Immunological data indicated that reactive oxygen species (ROS) modified human DNA induced high titer antibodies. In ELISA, serum antibodies from various cancer patients showed a higher recognition o f ROS-human DNA as compared to native DNA. Retarded mobility of the immune complex formed between IgG, isolated from cancer sera, and ROS-human DNA pr ovided convincing evidence for antigen-antibody interaction. Oxidative lesi ons in DNA of cancer patients were probed using anti-ROS-human DNA IgG. DNA from cancer patients were found to inhibit anti-ROS-human DNA IgG activity in the range of 40% to 57%. These binding results indicate the presence of oxidative lesions in the cancer patient's genome. (C) 1999 Elsevier Scienc e Ireland Ltd. All rights reserved.