The DNA molecules in cancer cells are the main targets of radiation therapy. To understand the underlying damaging processes during irradiations, simplified model systems can be investigated. Such a system, consisting out of DNA, radiation and water, and can be used to answer open questions. Two of the most fundamental ones are: „How does the quantity and quality of radiation damages to DNA change upon hydration?“ and „What is the ratio of direct and indirect DNA damage processes?“ These processes are difficult to distinguish because it is experimentally very challenging to access them simultaneously. Direct damage is caused by the interaction of high-energy photons and secondary low-energy electrons with DNA. In this process, the latter are abundant but cannot propagate very far in water. Therefore, they can only be studied in a vacuum environment. On the other hand, indirect damage result from processes involving water molecules, which are absent in classical vacuum experiments. To simultaneously access both types of damage, the mutually exclusive pair - water and vacuum - must be brought together. This has become possible recently by the advent of near-ambient pressure x-ray photoelectron spectroscopy. This technique enables us for the first time to monitor radiation induced chemical changes of DNA under water atmosphere. These experiments provided us, in combination with computer simulations, with the ability to distinguish direct and indirect damage, on the level of individual chemical bonds. The change of these chemical bonds is related to different types of DNA damage, such as strand breaks or base damage. They play an important role, in radiation chemistry, dosimetry and medicine, since they are linked to programmed cell death, genomic instability and carcinogenesis. Our results revealed a preferential formation of DNA strand-breaks by direct effects under vacuum conditions. In contrast, a dramatic shift towards DNA base damage and base release was observed for DNA in water. Here, the indirect damage effects, mediated by the interaction between the radiation with water became dominant.
The possibility to observe the chemical changes and damage formation under different hydration conditions directly is a huge step forward towards more efficient radiation therapy. The novel experimental approach allows us to study more complex biological systems, involving other biomolecules such as proteins, lipids, and additional precursors of reactive species, which are normally present in cells. Furthermore, it allows us to study more complex biological systems, involving other biomolecules such as proteins, lipids, and additional precursors of reactive species, which are normally present in cells.
In situ monitoring of the influence of water on DNA radiation damage by near-ambient pressure X-ray photoelectron spectroscopy
Marc Benjamin Hahn, P. M. Dietrich, Jörg Radnik
published in Communications Chemistry, Vol. 4, issue 1, page 50
BAM, department Materials Chemistry, division Surface Analysis and Interfacial Chemistry and division Physical and Chemical Analysis of Polymers