TY - THES A1 - Hahn, Marc Benjamin T1 - Quantifizierung der Schädigung von DNA in wässriger Lösung unter direkter Elektronenbestrahlung N2 - Bei der Behandlung von Krebs wird Strahlentherapie zur Zerstörung von Tumorzellen eingesetzt. Der zugrunde liegende Wirkmechanismus ist die durch ionisierende Strahlung verursachte Schädigung an Biomolekülen. Dabei kommt den Schädigungsprozessen an DNA aufgrund ihrer zentralen Rolle in Mutation und Zelltod eine besondere Bedeutung zu. Durch den hohen Wasseranteil in menschlichen Zellen findet ein Großteil der inelastischen Streuprozesse an Wassermolekülen statt und führt zur deren Radiolyse. Die so entstehenden Radiolyseprodukte sind für einen Großteil des Schadens an DNA verantwortlich. Ein detailliertes Verständnis der zugrunde liegenden molekularen Interaktion ist die Voraussetzung um effizientere Therapien zu entwickeln. Ziel dieser Arbeit ist es, die Schädigung von DNA durch ionisierende Strahlung in Abhängigkeit der inelastischen Streuevents und des Energieeintrags innerhalb des biologisch relevanten mikroskopischen Treffervolumens zu quantifizieren. Die Bestrahlungen müssen dazu in Flüssigkeit, unter Berücksichtigung der chemischen Umgebung durchgeführt werden, welche die indirekten Schäden vermittelt. Deshalb wurde eine neuartige Kombination aus Experiment und Monte- Carlo-Simulationen entworfen und angewandt. Um Elektronenbestrahlung flüssiger Lösungen innerhalb eines Rasterelektronenmikroskops zu ermöglichen, wurde ein Probenhalter mit einer für Elektronen durchlässigen Nanomembran entwickelt. So können Bestrahlungen an DNA, Proteinen, und Zellen bei verschiedenen pH-Werten, Salzkonzentrationen oder in Anwesenheit von Kosoluten durchgeführt werden. Für ein Modellsystem aus Plasmid-DNA in Wasser wurde damit die mittlere letale Dosis aus der Kombination der experimentellen Daten, Partikelstreusimulationen (Geant4-DNA) und Diffusionsberechnungen zu D1/2 = 1.7 ± 0.3 Gy bestimmt. Aus der Konvolution der Plasmidpositionen mit dem durch Elektronenstreusimulationen bestimmten ortsaufgelösten Energieeintrag wurde dessen Häufigkeitsverteilung im Targetvolumen der Plasmide sowie der mittlere mikroskopische letale Energieeintrag berechnet als E1/2 = 6 ± 4 eV . Es wurde gefolgert, dass weniger als zwei Ionisationsprozesse im sensitiven Targetvolumen der DNA im Mittel zu einem Einzelstrangbruch führen. Das für mikrodosimetrische Modellierungen wichtige Verhältnis von Einzelstrangbrüchen (SSB) zu Doppelstrangbrüchen (DSB) wurde als SSB : DSB = 12 : 1 bestimmt. Die vorgestellte Methode zur Bestimmung mikroskopischer Schaden-Dosis Relationen wurde auf weitere Klassen von Bestrahlungsexperimenten verallgemeinert. Dadurch ist die Methode unabhängig von der verwandten Primärstrahlung, der Probengeometrie und den Diffusionseigenschaften der untersuchten Moleküle anwendbar. So wird eine Vergleichbarkeit experimenteller Systeme mit inhomogenen Energieverteilungen erreicht, die bei ausschließlicher Betrachtung makroskopischer, gemittelter Größen nicht gegeben ist. Des weiteren wurden die Strahlenschutzfunktionen des kompatiblen Soluts Ectoine und sein Einfluss auf Wasser und Biomoleküle untersucht. Mittels Ramanspektroskopie wurde ein kon-zentrationsabhängiger Anstieg des Anteils der Kollektivmoden des Wassers der OH-Streckschwingungen und dessen Unabhängigkeit von der Natriumchloridkonzentration beobachtet. Molekulardynamik-Simulationen zeigten, dass die zwitterionischen Eigenschaften zur Bildung einer half-chair Konformation Ectoines führen. Die Wasserstoffbrückenbindungen in der ersten Hydrationshülle sind signifikant stabiler und besitzen höhere Lebensdauern als das Bulk-Wasser. Bestrahlung von DNA in Anwesenheit von 1 M Ectoine führt zu einer Erhöhung der Überlebensrate um den Faktor 1,41. Die Schutzfunktion wurde auf die Erhöhung des Streuquerschnitts niederenergetischer Elektronen an den akustischen Vibrationsmoden des Wasser durch Ectoine und seine Wirkung als OH-Radikalfänger zurückgeführt. Dies wurde mittels Ramanspektroskopie und Elektronenspinresonanzmessungen (ESR) nachgewiesen. N2 - To cure cancer radiation therapy is used to kill tumor cells. It is based on radiation induced damage to biomolecules. Especially DNA damage is of key interest due to its central role in apoptosis and mutation. Because of the high amount of water in biological tissue, most of the damage is caused by the secondary particles produced by the inelastic scattering of ionizing radiation and water. A detailed understanding of the underlying molecular processes under physiological conditions is the prerequisite to develop more efficient therapies. Goal of this work is to quantify the DNA damage caused by ionizing radiation in dependence of the inelastic scattering events and the energy deposit within the microscopic target volume of biological relevance. The irradiations have to be performed in liquid, under consideration of the chemical environment. Therefore, a new combination of experiment and Monte-Carlo simulations was developed and tested. To make it possible to irradiate liquids with electrons within scanning electron microscopes a new sample holder was constructed incorporating an electron transparent nanomembrane. It makes it possible to irradiate DNA, proteins or cells at different pH, salinity and in the presence of cosolutes. The median lethal dose for a model system of plasmid DNA and water was determined by the combination of experimental data, particle scattering simulations (Geant4-DNA) and Diffusion calculations as D1/2 = 1.7 ± 0.3 Gy. From the convolution of plasmid positions and the spatially resolved energy deposit, as determined by electron scattering simulations, the histogram of the energy deposit within the target volume of the plasmids and the microscopic median lethal energy deposit was calculated as E1/2 = 6 ± 4 eV . It could be deduced that on average less than two ionization events are sufficient to cause a single-strand-break. The relation of single- strand-breaks (SSB) to double-strand-breaks (DSB), which is of importance for microdosimetric modeling, was determined as SSB : DSB = 12 : 1. The presented method for the determination of microscopic dose-damage relations was further extended to be applicable for general irradiation experiments. It becomes independent of the type of primary radiation used, the experimental geometry, and the diffusional properties of the molecules under investigation. This way different experimental systems with varying, inhomogeneous energy deposit characteristics become comparable with each other, which is not possible when only macroscopic averaged values are taken into account. In addition, the radiation protection properties of the compatible solute ectoine, as well as ist influence on the water properties and biomolecules were investigated. Raman spectroscopy revealed a concentration dependent increase of the collective water modes in the OH-stretching region, which was found to be independent of the sodium chloride concentration. Molecular dynamic simulations showed that the zwitterionic properties of ectoine lead to its half-chair conformation. The hydrogen bonds in the first hydration shell are more stable and have an increased lifetime compared to the bulk water. Irradiation experiments with DNA in the presence of 1 M ectoine revealed an increase of the survival rate by a factor of 1.41 as compared to the absence of ectoine. The protective properties of ectoine result from the increase of the inelastic scattering probabilities of low energy electrons at the acoustic vibrational modes of water and its properties as OH-radical scavenger. This was shown by Raman spectroscopy and electron paramagnetic resonance measurements (EPR). KW - DNA KW - Radiation KW - Radiation damage KW - Dosimetry KW - Microdosimetry KW - DNA damage KW - DNA radiation damage KW - Low energy electrons KW - Electron irradiation KW - Hydroxyl radicals KW - Ectoine KW - Ectoine protein interaction KW - Ectoine DNA interaction KW - Ectoine radiation protection KW - Ectoine salt KW - Cancer therapy KW - Radiation therapy KW - Ectoin PY - 2018 UR - https://nbn-resolving.org/urn:nbn:de:kobv:188-fudissthesis000000106497-4 UR - http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000106497 SP - 1 EP - 108 CY - Berlin AN - OPUS4-44510 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hahn, Marc Benjamin A1 - Dietrich, P. M. A1 - Radnik, Jörg T1 - In situ monitoring of the influence of water on DNA radiation damage by near-ambient pressure X-ray photoelectron spectroscopy JF - Communications Chemistry N2 - Ionizing radiation damage to DNA plays a fundamental role in cancer therapy. X-ray photoelectron-spectroscopy (XPS) allows simultaneous irradiation and damage monitoring. Although water radiolysis is essential for radiation damage, all previous XPS studies were performed in vacuum. Here we present near-ambient-pressure XPS xperiments to directly measure DNA damage under water atmosphere. They permit in-situ monitoring of the effects of radicals on fully hydrated double-stranded DNA. The results allow us to distinguish direct damage, by photons and secondary low-energy electrons (LEE), from damage by hydroxyl radicals or hydration induced modifications of damage pathways. The exposure of dry DNA to x-rays leads to strand-breaks at the sugar-phosphate backbone, while deoxyribose and nucleobases are less affected. In contrast, a strong increase of DNA damage is observed in water, where OH-radicals are produced. In consequence, base damage and base release become predominant, even though the number of strand-breaks increases further. KW - DNA KW - XPS KW - NAP-XPS KW - Radiation damage KW - Single-strand break (SSB) KW - Double-strand break (DSB) KW - Xray KW - OH radical KW - Hydroxyl radical KW - LEE KW - Low energy electrons KW - Dosimetry KW - Geant4 KW - Geant4-DNA KW - TOPAS KW - TOPAS-nbio KW - Microdosimetry KW - DNA radiation damage KW - Direct damage KW - Indirect damage KW - Quasi-direct damage KW - Hydration shell KW - Dry DNA KW - Hydrated DNA KW - ROS KW - Radical KW - Reactive oxygen species KW - Net-ionization reaction KW - Radiation therapy KW - Cancer therapy KW - Xray photo electron spectrocopy KW - Near ambient pressure xray photo electron spectroscopy KW - Base damage KW - Base loss KW - Dissociative electron transfer (DET) KW - Dissociative electron attachment (DEA) KW - Hydrated electron KW - Prehydrated electron KW - Ionization KW - PES PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-524060 DO - https://doi.org/10.1038/s42004-021-00487-1 SN - 2399-3669 VL - 4 IS - 1 SP - 50 PB - Springer Nature CY - London AN - OPUS4-52406 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Dietrich, P. M. A1 - Radnik, Jörg T1 - The change of DNA radiation damage upon hydration: In-situ observations by near-ambient-pressure XPS N2 - Ionizing radiation damage to DNA plays a fundamental role in cancer therapy. X-ray photoelectron-spectroscopy (XPS) allows simultaneous irradiation and damage monitoring. Although water radiolysis is essential for radiation damage, all previous XPS studies were performed in vacuum. Here we present near-ambient-pressure XPS experiments to directly measure DNA damage under water atmosphere. They permit in-situ monitoring of the effects of radicals on fully hydrated double-stranded DNA. The results allow us to distinguish direct damage, by photons and secondary low-energy electrons (LEE), from damage by hydroxyl radicals or hydration induced modifications of damage pathways. The exposure of dry DNA to x-rays leads to strand-breaks at the sugar-phosphate backbone, while deoxyribose and nucleobases are less affected. In contrast, a strong increase of DNA damage is observed in water, where OH-radicals are produced. In consequence, base damage and base release become predominant, even though the number of strand-breaks increases further. T2 - #RSCposter 2023 CY - Online meeting DA - 28.02.2023 KW - Cancer treatment KW - DNA KW - Dosimetry KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - TOPAS KW - TOPAS-nbio KW - particle scattering KW - Simulation KW - Radiolysis KW - Radiation therapy KW - Radiotherapy KW - LEE KW - Low energy electrons KW - MCS KW - Base damage KW - Base loss KW - DNA radiation damage KW - Direct damage KW - Dissociative electron transfer (DET) KW - Dissociative electron attachment (DEA) KW - Double-strand break (DSB) KW - Hydrated DNA KW - Hydrated electron KW - Ionization KW - Hydration shell KW - Hydroxyl radical KW - Indirect damage KW - Microdosimetry KW - NAP-XPS KW - Near ambient pressure xray photo electron spectroscopy KW - Net-ionization reaction KW - OH radical KW - PES KW - Prehydrated electron KW - Quasi-direct damage KW - Radiation damage KW - Radical KW - Reactive oxygen species KW - ROS KW - Single-strand break (SSB) KW - XPS KW - Xray KW - Xray photo electron spectrocopy KW - presolvated electron PY - 2023 UR - https://www.nature.com/articles/s42004-021-00487-1 AN - OPUS4-57063 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Hallier, Dorothea C. A1 - Smales, Glen Jacob A1 - Seitz, H. T1 - Extending Bio-SAXS measurements of Single-Stranded DNA-Binding Proteins: Radiation Protection of G5P by Cosolutes N2 - Small-angle X-ray scattering (SAXS) can be used for structural de- termination of biological macromolecules and polymers in their na- tive states. To improve the reliability of such experiments, the re- duction of radiation damage occurring from exposure to X-rays is needed.One method, is the use of scavenger molecules that protect macromolecules against radicals produced by radiation exposure.In this study we investigate the feasibility to apply the compatible solute, osmolyte and radiation protector Ectoine (THP(B)) as a scavenger throughout SAXS measurements of single-stranded DNA-binding protein Gene-V Protein (G5P/GVP). Therefore we monitor the radiation induced changes of G5P during bio-SAXS. The resulting microscopic energy-damage relation was determined by particle scattering simu- lations with TOPAS/Geant4. The results are interpreted in terms of radical scavenging as well as post-irradiation effects, related to preferential-exclusion from the protein surface. Thus, Ectoine provides an non-disturbing way to improve structure-determination of proteins via bio-SAXS in future studies. T2 - MultiChem Conference 2023 CY - Prague, Czech Republic DA - 26.04.2023 KW - Bio-SAXS KW - BioSAXS KW - Compatible solute KW - Cosolute KW - DNA KW - Dosimetry KW - Ectoin KW - Ectoine KW - Ectoin KW - G5P KW - GVP KW - Geant4 KW - Geant4-DNA KW - Gene five protein KW - Hydroxyectoine KW - Ionizing radiation damage KW - LEE KW - McSAS3 KW - Microdosimetry KW - Monte-Carlo simulations KW - OH Radical KW - OH radical scavenger KW - Osmolyte KW - Particle scattering simulations KW - Protein KW - Protein unfolding KW - Proteins KW - ROS KW - Radiation damage KW - Radical Scavenger KW - Radical scavenger KW - SAXS KW - Single-stranded DNA-binding proteins KW - Small-angle xray scattering KW - Topas KW - Topas-MC KW - Topas-nBio KW - X-ray scattering KW - ssDNA KW - Median lethal energy deposit PY - 2023 AN - OPUS4-57407 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hallier, Dorothea C. A1 - Smales, Glen Jacob A1 - Seitz, H. A1 - Hahn, Marc Benjamin T1 - Inside back cover for the article "Bio-SAXS of single-stranded DNA-binding proteins: Radiation protection by the compatible solute ectoine" JF - Physical chemistry chemical physics (PCCP) N2 - Showcasing research from the Federal Institute for Material Research and Testing Berlin and Fraunhofer Institute for Celltherapy and Immunology Branch Bioanalytics and Bioprocesses Potsdam. Bio-SAXS of single-stranded DNA-binding proteins: Radiation protection by the compatible solute ectoine. We aimed to increase the possible undisturbed exposure time during bio-SAXS measurements of single-stranded DNA-binding proteins. Therefore small angle X-ray scattering was performed on Gene-V Protein (G5P/GVP), which is involved in DNA repair processes. To achieve this, irradiations were performed in presence and absence of the hydroxyl-radical scavenger and osmolyte Ectoine, which showed efficient radiation protection and prevented protein aggregation, thus allows for a non-disturbing way to improve structure-determination of biomolecules. KW - Bio-SAXS KW - BioSAXS KW - Cosolute KW - DNA KW - Dosimetry KW - Ectoin KW - Ectoine KW - G5P KW - GVP KW - Geant4 KW - Geant4-DNA KW - Ionizing radiation damage KW - LEE KW - McSAS3 KW - Microdosimetry KW - Monte-Carlo simulations KW - OH Radical KW - OH radical scavenger KW - Protein KW - Protein unfolding KW - Radiation damage KW - Radical Scavenger KW - SAXS KW - Single-stranded DNA-binding proteins KW - Small-angle xray scattering KW - Topas-MC KW - Topas-nBio KW - TopasMC KW - X-ray scattering KW - Particle scatterin simulations KW - ssDNA PY - 2023 DO - https://doi.org/10.1039/D3CP90056H SN - 1463-9076 SN - 1463-9084 VL - 25 IS - 7 SP - 5889 PB - Royal Society of Chemistry CY - Cambridge AN - OPUS4-57006 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hahn, Marc Benjamin A1 - Smales, Glen Jacob A1 - Seitz, H. A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - Ectoine interaction with DNA: Influence on ultraviolet radiation damage JF - Physical Chemistry Chemical Physics N2 - Ectoine is a small zwitterionic osmolyte and compatible solute, which does not interfere with cell metabolism even at molar concentrations. Plasmid DNA (pUC19) was irradiated with ultraviolet radiation (UV-C at 266 nm) under quasi physiological conditions (PBS) and in pure water in the presence and absence of ectoine (THP(B)) and hydroxyectoine (THP(A)). Different types of UV induced DNA damage were analysed: DNA single-strand breaks (SSBs), abasic sites and cyclobutane pyrimidine dimers (CPDs). A complex interplay between these factors was observed with respect to the nature and occurrence of DNA damage with 266 nm photons. In PBS, the cosolutes showed efficient protection against base damage, whilst in pure water, a dramatic shift from SSB damage to base damage was observed when cosolutes were added. To test whether these effects are caused by ectoine binding to DNA, further experiments were conducted: small-angle X-ray scattering (SAXS), surface-plasmon resonance (SPR) measurements and Raman spectroscopy. The results show, for the first time, a close interaction between ectoine and DNA. This is in stark contrast to the assumption made by preferential exclusion models, which are often used to interpret the behaviour of compatible solutes within cells and with biomolecules. It is tentatively proposed that the alterations of UV damage to DNA are attributed to ectoine influence on nucleobases through the direct interaction between ectoine and DNA. KW - Ectoine KW - DNA KW - Radiation damage KW - Radiation protection KW - SSB KW - DNA damage KW - DNA protection KW - Compatible solute KW - Zwitterion KW - Hydroxyectoine KW - Salt KW - PBS KW - UV absorption KW - DNA strand-break KW - DNA base damage KW - Ectoine UV absorption KW - Ectoine DNA protection KW - Excited states KW - UV irradiation KW - UV-A KW - UV-B KW - UV-C KW - 266nm KW - UV photons KW - Ectoine-DNA binding KW - Raman spectroscopy KW - UV-Vis KW - Radical scavenger KW - OH scavenger KW - Hydroxyl radicals KW - CPD KW - Abasic site KW - Agarose gel electrophorese KW - SYBR gold KW - DNA melting temperature KW - Counterions KW - Preferential exclusion KW - Cancer KW - Therapy KW - UV protection KW - Sunscreen PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-505772 DO - https://doi.org/10.1039/d0cp00092b SN - 1463-9076 SN - 1463-9084 VL - 22 IS - 13 SP - 6984 EP - 6992 PB - Royal Society of Chemistry CY - Cambridge AN - OPUS4-50577 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Cordsmeier, Leo A1 - Hahn, Marc Benjamin T1 - DNA Stability in Biodosimetry, Pharmacy and DNA Based Data-Storage: Optimal Storage and Handling Conditions JF - ChemBioChem N2 - DNA long-term stability and integrity is of importance for applications in DNA based bio-dosimetry, data-storage, pharmaceutical quality-control, donor insemination and DNA based functional nanomaterials. Standard protocols for these applications involve repeated freeze-thaw cycles of the DNA, which can cause detrimental damage to the nucleobases, as well as the sugar-phosphate backbone and therefore the whole molecule. Throughout the literature three hypotheses can be found about the underlying mechanisms occurring during freeze-thaw cycles. It is hypothesized that DNA single-strand breaks during freezing can be induced by mechanical stress leading to shearing of the DNA molecule, by acidic pH causing damage through depurination and beta elimination or by the presence of metal ions catalyzing oxidative damage via reactive oxygen species (ROS). Here we test these hypotheses under well defined conditions with plasmid DNA pUC19 in high-purity buffer (1xPBS) at physiological salt and pH 7.4 conditions, under pH 6 and in the presence of metal ions in combination with the radical scavengers DMSO and Ectoine. The results show for the 2686 bp long plasmid DNA, that neither mechanical stress, nor pH 6 lead to degradation during repeated freeze-thaw cycles. In contrast, the presence of metal ions (Fe2+) leads to degradation of DNA via the production of radical species. KW - DNA KW - DNA stability KW - Pharmacy KW - Reference material KW - pUC19 KW - Strand break KW - SSB KW - Dosimetry KW - Biodosimetry KW - Biologisches Dosimeter KW - DNA Dosimeter KW - Quality control KW - Plasmid DNA KW - DNA data storage KW - Nucleobase KW - Base damage KW - Base loss KW - DNA degradation KW - Metal ions KW - ROS KW - OH radical KW - Fenton Reaction KW - H2O2 KW - DNA based data storage KW - Freezing KW - Thawing KW - Mechanical stress KW - pH KW - Beta elimination KW - Ectoine KW - Ectoin KW - THP(B) KW - Radical scavenger KW - DMSO KW - Buffer KW - lN2 KW - DNA vortexing KW - AGE KW - SYBR Gold KW - Gel electrophoresis KW - DNA long term storage KW - DNA reference material PY - 2022 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-557148 DO - https://doi.org/10.1002/cbic.202200391 SP - 1 EP - 9 PB - Wiley-VCH GmbH AN - OPUS4-55714 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Radiation biophysics N2 - We give an overview about our work related to radiation damage to DNA, proteins, and DNA-protiren complexes damage. Hereby the focus lies on the combination of experiments and Geant4 particle scattering simulations to understand effects in plasmid DNA pUC19, Oligos, and G5P protein. T2 - Project overview CY - Berlin, Germany DA - 27.09.2023 KW - DNA KW - Dosimetry KW - Proteins KW - Radiation damage KW - G5P KW - Microdosimetry KW - Ionizing radiation KW - Geant4 KW - TOPAS KW - TOPAS-nBio KW - Geant4-DNA KW - LEE KW - OH KW - Hydroxyl radical PY - 2023 AN - OPUS4-58742 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hahn, Marc Benjamin A1 - Zutta Villate, J. M. ED - Zutta Villate, J. M. T1 - Combined cell and nanoparticle models for TOPAS to study radiation dose enhancement in cell organelles JF - Scientific Reports N2 - Dose enhancement by gold nanoparticles (AuNP) increases the biological effectiveness of Radiation damage in biomolecules and tissue. To apply them effectively during cancer therapy their influence on the locally delivered dose has to be determined. Hereby, the AuNP locations strongly influence the energy deposit in the nucleus, mitochondria, membrane and the cytosol of the targeted cells. To estimate these effects, particle scattering simulations are applied. In general, different approaches for modeling the AuNP and their distribution within the cell are possible. In this work, two newly developed continuous and discrete-geometric models for simulations of AuNP in cells are presented. These models are applicable to simulations of internal emitters and external radiation sources. Most of the current studies on AuNP focus on external beam therapy. In contrast, we apply the presented models in Monte-Carlo particle scattering simulations to characterize the energy deposit in cell organelles by radioactive 198AuNP. They emit beta and gamma rays and are therefore considered for applications with solid tumors. Differences in local dose enhancement between randomly distributed and nucleus targeted nanoparticles are compared. Hereby nucleus targeted nanoparticels showed a strong local dose enhancement in the radio sensitive nucleus. These results are the foundation for future experimental work which aims to obtain a mechanistic understanding of cell death induced by radioactive 198Au. KW - AuNP KW - Beta decay KW - Brachytherapy KW - Cancer treatment KW - DNA KW - DNA damage KW - Dosimetry KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Gold Nanoparticles KW - LEE KW - MCS KW - Microdosimetry KW - Monte-Carlo simulation KW - NP KW - Ectoine KW - OH radicals KW - Radiation damage KW - Radiationtherapy KW - Radioactive decay KW - Simulation KW - Beta particle KW - Clustered nanoparticles KW - Gamma ray KW - Low energy electrons KW - Particle scattering KW - Radiolysis KW - Livermore model KW - Penelope model KW - TOPAS KW - TOPAS-nbio PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-523276 DO - https://doi.org/10.1038/s41598-021-85964-2 SN - 2045-2322 VL - 11 IS - 1 SP - 6721 PB - Springer Nature AN - OPUS4-52327 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Dietrich, P. M. A1 - Radnik, Jörg A1 - Solomun, Tihomir A1 - Hallier, Dorothea C. A1 - Seitz, H. T1 - The change of dna and protein radiation damage upon hydration: in-situ observations by near-ambient-pressure xps N2 - X-ray photoelectron-spectroscopy (XPS) allows simultaneous irradiation and damage monitoring. Although water radiolysis is essential for radiation damage, all previous XPS studies were performed in vacuum. Here we present near-ambient-pressure XPS experiments to directly measure DNA damage under water atmosphere. They permit in-situ monitoring of the effects of radicals on fully hydrated double-stranded DNA. Our results allow us to distinguish direct damage, by photons and secondary low-energy electrons (LEE), from damage by hydroxyl radicals or hydration induced modifications of damage pathways. The exposure of dry DNA to x-rays leads to strand-breaks at the sugar-phosphate backbone, while deoxyribose and nucleobases are less affected. In contrast, a strong increase of DNA damage is observed in water, where OH-radicals are produced. In consequence, base damage and base release become predominant, even though the number of strand-breaks increases further. Furthermore, first data about the degradation of single-stranded DNA binding-proteins (G5P / GV5 and hmtSSB) under vacuum and NAP-XPS conditions are presented. T2 - AVS69 CY - Portland, USA DA - 05.11.2023 KW - Base damage KW - Base loss KW - Cancer treatment KW - DNA KW - Protein KW - Proteins KW - Geant4 KW - Dosimetry KW - Microdosimetry KW - NAP-XPS KW - Xray photo electron spectrocopy KW - Radiation damage KW - Geant4-DNA KW - G5P KW - GVP KW - Hydroxyl radical KW - LEE KW - DEA KW - DET KW - ROS KW - Prehydrated electron KW - TOPAS KW - Near ambient pressure xray photo electron spectroscopy KW - SSB KW - DSB KW - Single-strand break (SSB) KW - ESCA KW - Single-stranded DNA-binding proteins KW - Reactive oxygen species PY - 2023 AN - OPUS4-58761 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -