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Dissertation / PhD Thesis | PUBDB-2024-07705 |
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2024
Abstract: DNA damage is generally considered to be the most common and most important type of lesions in cells caused by ionizing radiation. While DNA damage caused by ionizing radiation poses serious risks to human health, it also makes radiation therapy a powerful tool for killing cancer cells and saving lives. For these reasons, a great deal of research has focused on radiation-induced processes within DNA. However, most of this work has been carried out in the condensed phase, which cannot remove the influence of the surrounding environment. In order to investigate the consequences of direct interaction of DNA with ionizing radiation at the molecular scale, we have irradiated a self-complementary DNA sequence in the gas phase with synchrotron radiation or ion beams, and analyzed the resulting product ions by mass spectrometry. Thanks to ion mobility spectrometry, we have established that deprotonated double strands of this sequence indeed form a double helix that is stable in an ion trap, if the charge state is higher than 5-. Then, we have investigated the consequences of specific photoabsorption occurring at the DNA oligonucleotide backbone in the gas phase. By monitoring non-dissociative single electron detachment from deprotonated precursors as a function of photon energy around the phosphorus K-edge, we have identified the X-ray spectral signature of selective photoabsorption at the phosphorus atoms located only in the backbone. We also detected abundant nucleobase fragment cations resulting from multiple electron detachment and thus demonstrated the charge, energy and hydrogen transfer from the backbone to the nucleobases. In the final part of the thesis, we present the results of irradiation of the DNA oligonucleotides by carbon ions in the gas phase. We have observed similar non-dissociative single electron detachment and similarly abundant positive fragment ions after carbon ion impact as in the case of irradiation by X-ray photons. More importantly, we have successfully irradiated a helical DNA double strand in the gas phase for the first time. 70% of the resulting ionic products come from non-dissociative single electron detachment, which is much higher than the case of single strands. Therefore, direct ionization of a DNA double helix after interaction with a single carbon ion does not lead to separation of the strands, which has important implications regarding DNA damage, notably in the context of hadrontherapy.
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