X-ray and UV Radiation Damage of dsDNA/Protein Complexes

Simple SummaryOne of the most common diseases in the world is cancer. The development of an appropriate treatment pathway for cancer patients seems to be crucial to fight this disease. Therefore, solving the problem that affects more and more people in an aging society is crucial. The study presents the results of radiation and photochemical damage to DNA interacting with proteins (specifically/non-specifically). The obtained results of the analysis of photoliths and radiolites by means of the LC-MS technique allowed to identify possible mechanisms of degradation of DNA interacting with proteins. Results suggest the protective action of protein against hydroxyl radicals or solvated electrons and increased damaging effect when sensitized DNA is irradiated by UV light (280 or 320 nm) compared to the DNA alone (without protein interaction).AbstractRadiation and photodynamic therapies are used for cancer treatment by targeting DNA. However, efficiency is limited due to physico-chemical processes and the insensitivity of native nucleobases to damage. Thus, incorporation of radio- and photosensitizers into these therapies should increase both efficacy and the yield of DNA damage. To date, studies of sensitization processes have been performed on simple model systems, e.g., buffered solutions of dsDNA or sensitizers alone. To fully understand the sensitization processes and to be able to develop new efficient sensitizers in the future, well established model systems are necessary. In the cell environment, DNA tightly interacts with proteins and incorporating this interaction is necessary to fully understand the DNA sensitization process. In this work, we used dsDNA/protein complexes labeled with photo- and radiosensitizers and investigated degradation pathways using LC-MS and HPLC after X-ray or UV radiation.