TY - CONF A1 - Hahn, Marc Benjamin A1 - Meyer, Susan A1 - Solomun, Tihomir A1 - Kunte, Hans-Jörg A1 - Sturm, Heinz T1 - Electron irradiation of biomolecules under physiological conditions: Experimental realization and microdosimetric calculations N2 - In the last years, secondary low-energy electrons (LEE) emerged as important, if not predominant, reductive pathway in ionizing damage of biomolecules. These electrons are created in copious amount as result of inelastic scattering of high energy radiation at water. Until now, all experiments the quantification of the effects of LEEs on the biomolecular damage was either performed in vacuum with LEE sources or with DNA on surfaces in humid atmosphere. We present a new experimental setup to irradiate biomolecules with electrons under physiological conditions. In combination with monte carlo simulations this setup makes it possible to determine microdosimetric quantities for biomolecules in liquid environment under electron irradiation. This opens up new possibilities in radiation research to access the LEE damage under well defined physiological condition, for more complex systems, such as DNA-Protein complexes and even living cells. T2 - 14th International Congress of the International Radiation Protection Association CY - Cape Town, South Africa DA - 09.05.2016 KW - DNA KW - Dosimetry KW - Microdosimetry KW - Geant4 KW - Low energy electrons KW - Radicals KW - Radiation damage KW - Polymers PY - 2016 AN - OPUS4-36399 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hahn, Marc Benjamin A1 - Meyer, Susann A1 - Kunte, Hans-Jörg A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - Measurements and simulations of microscopic damage to DNA in water by 30 keV electrons: A general approach applicable to other radiation sources and biological targets N2 - The determination of the microscopic dose-damage relationship for DNA in an aqueous environment is of a fundamental interest for dosimetry and applications in radiation therapy and protection. We combine geant4 particle-scattering simulations in water with calculations concerning the movement of biomolecules to obtain the energy deposit in the biologically relevant nanoscopic volume. We juxtaposition these results to the experimentally determined damage to obtain the dose-damage relationship at a molecular level. This approach is tested for an experimentally challenging system concerning the direct irradiation of plasmid DNA (pUC19) in water with electrons as primary particles. Here a microscopic target model for the plasmid DNA based on the relation of lineal energy and radiation quality is used to calculate the effective target volume. It was found that on average fewer than two ionizations within a 7.5-nm radius around the sugar-phosphate backbone are sufficient to cause a single strand break, with a corresponding median lethal energy deposit being E1/2=6±4 eV. The presented method is applicable for ionizing radiation (e.g., γ rays, x rays, and electrons) and a variety of targets, such as DNA, proteins, or cells. KW - DNA KW - Radiation damage KW - Dosimetry KW - DNA radiation damage KW - Single-strand break (SSB) KW - Double-strand break (DSB) KW - Low energy electrons KW - Monte Carlo simulation KW - Radiation damage to biomolecules KW - Plasmid DNA in water KW - Lethal dose KW - Solutions (pH, salinity, cosolutes) KW - Geant4 KW - Microdosimetry PY - 2017 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-404244 DO - https://doi.org/10.1103/PhysRevE.95.052419 SN - 2470-0045 SN - 2470-0053 VL - 95 IS - 5 SP - 052419-1 EP - 052419-8 PB - American Physical Society CY - USA AN - OPUS4-40424 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Solomun, Tihomir A1 - Meyer, Susann A1 - Kunte, Hans-Jörg A1 - Schröter, Maria-Astrid A1 - Sturm, Heinz T1 - Development of a standard procedure for the irradiation of biomolecules N2 - In dosimetry the determination of the effectiveness of the damaging processes is standardized and accounted for by the radiation and tissue weighting factor. For the underlying constituents of the tissue, that is the various biomolecules, such a systematic approach doesn't exist. This makes it difficult to compare results obtained under different experimental conditions. In the following work, we will describe a method to obtain comparable values for the radiation-biomolecule interaction, measured under different conditions. This approach can lead to standardization of dosedamage relationship at the molecular level. Such approach is necessary for a better understanding of the relations between the damage of the single constituents of biological tissue and the whole – finally gaining a more complete picture of irradiation damage. T2 - 14th International Congress of the International Raditation Protection Association (IRPA) CY - Cape Town, South Africa DA - 09.05.2016 KW - Dosimetry PY - 2017 VL - 14 SP - 1 EP - 5 AN - OPUS4-41164 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Direct electron irradiation of DNA in fully aqueous environment: Microscopic dose determination in combination with Monte-Carlo simulations N2 - Introduction: Ionizing radiation & DNA damage Experimental setup: Direct electron irradiation of DNA in liquid Monte-Carlo simulations: Electron scattering & diffusion Application: Radiation protection by compatible solutes T2 - Seminarvortrag im Joint Ultrafast Dynamics Laboratory in Solution and at Interfaces CY - Helmholtz-Zentrum Berlin, Germany DA - 14.06.2017 KW - DNA KW - Ectoine KW - Microdosimetry KW - Dosimetry KW - Radiation damage KW - Compatible solutes KW - Low energy electrons KW - Ionizing radiation KW - OH radical KW - Hydroxyl radicals KW - Prehydrated electrons KW - Radiation therapy KW - Cancer KW - Cancer therapy KW - Radiation protection KW - Proteins KW - Monte carlo simulations KW - Geant4 KW - Electron scattering PY - 2017 AN - OPUS4-42620 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Solomun, Tihomir A1 - Schroeter, Maria-Astrid A1 - Sturm, Heinz T1 - From sensing to dosimetry: Immobilized single-stranded DNA on surfaces as versatile sensor for protein activity and irradiation damage N2 - We report on the design, preparation and application of immobilized Oligonucleotides as biological sensors for dosimetry and protein activity. Oligonucleotides can be custom tailored in terms of sequence and length to the needs of the specific application. The preparation can be scaled from small lab-scales to higher output via spotting technology on various surfaces such as glass, silicon-dioxide or gold. They can be applied for the sensing of DNA-protein interaction and surface-plasmon resonance to detect the influence of cosolutes on the protein activity. This can be applied in the testing of pharmaceutical or cosmsetic applications and incorporated in microfluidic devices. Other important use cases are the usage in dosimetric application where the oligonucleotides are subjected to ionizing radiation. They can directly act as a sensor for biological damage which is detected and quantified by the subsequent hybridization of complementary strands who carry a fluorescence dye. The quantification can be performed by an array scanner or fluorescence microscope. Investigation on a molecular level can be performed with the AFM-IR technique. Applications are calibration of radiation sources and the investigation of interaction of ionizing radiation with biomolecules. T2 - Euromat 2017 CY - Thessaloniki, Greece DA - 17.09.2017 KW - DNA KW - Protein KW - Dosimetry KW - Radiation damage KW - SPR KW - Surface modification PY - 2017 AN - OPUS4-42619 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - DNA strand break induction by secondary radiation products: damage yields of OH-radicals, low energy electrons and prehydrated electrons N2 - The damage caused by ionizing radiation to biomolecules, especially DNA, is the reason to treat cancer via radiation therapy. A better understanding of the molecular processes and the quantification of the various damaging mechanisms is the prerequisit to develope efficient therapies. Hereby the understanding of the processes involved in the damage to DNA are of key interest due to its central role in reproduction and mutation. Due to the high amount of water in biological tissue, most of the damage is caused by the secondary particles produced by the interaction of the IR with water. Thereby a multitude of species are produced, e.g. kinetic low energy electrons, prehydrated electrons, OH-radicals and ions. The quantification of the contribution to DNA damage of the various species is of interest. Here we present an experimental approach to disentangle their relative DNA strand break yield. Plasmid DNA is irradiated in water with electrons under the presence of different scavengers. With the presented method it will be possible to reveal the relative contributions of OH-radicals, low energy electrons and prehydrated electrons to the DNA single and double strand break yield. T2 - Radiation Research Conference 2017 CY - Cancun, Mexico DA - 15.10.2017 KW - DNA KW - Dosimetry KW - Radiation damage KW - low energy electrons KW - OH radicals KW - Prehydrated electrons KW - LEE KW - Geant4 KW - Hydroxyl radicals KW - Radiation protection KW - Biomolecules KW - Microdosimetry PY - 2017 AN - OPUS4-42617 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Meyer, Susann A1 - Schroeter, Maria-Astrid A1 - Kunte, Hans-Jörg A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - Electron beam therapy: Microdosimetric calculations for the quantification of fundamental damaging processes N2 - Electron beam therpy is used to treat tumor cells by irradiation with high energy electrons (HEE). The irradiation is performed by medical linear accelerators. By interaction of the HEE with the irradiated tissue a broad spectra of secondary electrons and water dissoziation products is generated. These products interact with biomolecules, especially DNA, by various processes. The disentanglement of the resulting direct- and indirect damage to DNA and other cellular components is still under debate. To increase the efficiency of future therapies a better understanding of the microscopic damaging processes is highly important. Especially the various contributions of the secondary species produced, such as low energy electrons (LEE) and radicals is far from understood and quantified. To increase the understanding we present a combination of a microdosimetric simulations and experiments to quantify the damage by means of electron scattering and diffusion simulations within the Geant4-DNA framework. In combination with in-liquid irradiation of plasmid DNA it possible to determine microdosimetric quantities for biomolecules in liquid environment. The presented method was applied to the irradiation of plasmid DNA (pUC19) in water. This opens up new possibilities in radiation research to quantify the dosage-damage relationship for microscopic plasmid volumes under well defined physiological condition. T2 - IWBBIO17 CY - Granada. Spain DA - 25.04.2017 KW - DNA KW - Dosimetry KW - Monte-Carlo simulation KW - Electron irradiation KW - Microdosimetry PY - 2017 AN - OPUS4-40043 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - 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 - CONF A1 - Hahn, Marc Benjamin A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - Standard procedure for the irradiation of biomolecules with radiation of different linear energy transfer N2 - The damage caused by ionizing radiation to DNA and proteins is the reason to treat cancer by radiation therapy. A better understanding of the molecular processes and quantification of the different damaging mechanisms is the prerequisite to develop more efficient therapies. Hereby the understanding of the processes involved in the damage to DNA are of key interest due to its central role in reproduction and mutation. For radiation with low linear energy transfer (LET), most of the damage is caused by the secondary particles produced by scattering of the ionizing radiation with water. Thereby a multitude of species are produced, whereby especially kinetic low energy electrons, prehydrated electrons, OH-radicals and ions are of importance. With higher LET the relative amount of the direct damaging effects increases. This is especially important considering the increased usage of high LET nucleons in radiation therapy. Therefore, the quantification of the contribution to DNA damage of direct and indirect effects and the different secondary species is of high interest due to the increase of radio biological efficiency when applying high LET radiation. Here we present an approach to investigate the relative contributions to DNA strand break yield for radiation of different LET within a single electron microscope in combination with electron scattering simulations. T2 - XI International Radiation Protection Association Conference 2018 America CY - Havanna, Cuba DA - 16.04.2018 KW - Dosimetry KW - Linear energy transfer KW - Radiation damage KW - LET KW - Electron irradiation KW - Low energy electrons KW - Hydroxyl radicals KW - DEA KW - DET KW - Microdosimetry KW - Geant4 KW - Electron irradiation of DNA KW - DNA PY - 2018 VL - 2018 SP - 1 EP - 5 AN - OPUS4-44848 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Quantifizierung der Schädigung von DNA in wässriger Lösung unter direkter Elektronenbestrahlung 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 most important results of this work are as follows: 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 D0.5=(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 E0.5=6+-4eV. 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 its influence on the water properties and biomolecules were investigated. %In addition, the influence of the compatible solute ectoine on water, biomolecules and its radiation protection properties 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 1M 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). T2 - Vortrag CY - Freie Universität Berlin, Germany DA - 14.02.2018 KW - DNA KW - Radiation damage KW - Ionizing radiation KW - DNA strand break KW - Dosimetry KW - Microdosimetry KW - Ectoine KW - Ectoine radiation protection KW - Salt KW - Water PY - 2018 AN - OPUS4-44280 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - Determination of the Microscopic Dose-Damage Relation for Radiation of different Linear Energy Transfer N2 - The determination of the microscopic dose-damage relationship for DNA in an aqueous environment is of a fundamental interest for dosimetry and applications in radiation therapy and protection. We combine geant4 particle-scattering simulations in water with calculations concerning the movement of biomolecules to obtain the energy deposit in the biologically relevant nanoscopic volume.[1] We juxtaposition these results to the experimentally determined damage to obtain the microscopic dose-damage relationship at a molecular level. This approach is tested for an experimentally challenging system concerning the direct irradiation of plasmid DNA (pUC19) in water with electrons as primary particles.[2] Here a microscopic target model for the plasmid DNA based on the relation of lineal energy and radiation quality is used to calculate the effective target volume. It was found that on average fewer than two ionizations within a 7.5-nm radius around the sugar-phosphate backbone are sufficient to cause a single strand break, with a corresponding median lethal energy deposit being E1/2=6±4 eV.[1] The presented method is applicable for ionizing radiation (e.g., γ rays, x rays, and electrons) and a variety of targets, such as DNA, proteins, or cells. [1] Hahn, M. B., Meyer, S., Kunte, H.-J., Solomun, T. & Sturm, H. Measurements and simulations of microscopic damage to DNA in water by 30 keV electrons: A general approach applicable to other radiation sources and biological targets. Phys. Rev. E 95, 052419 (2017). [2] Hahn, M. B. et al. Direct electron irradiation of DNA in a fully aqueous environment. Damage determination in combination with Monte Carlo simulations. Phys. Chem. Chem. Phys. 19, 1798–1805 (2017). T2 - DYSON 2018 CY - Potsdam, Germany DA - 08.10.2018 KW - DNA KW - Dosimetry KW - Electron irradiation KW - Geant4 KW - Hydroxyl radical KW - LET KW - Linear energy transfer KW - Low energy electrons KW - MCS KW - Microdosimetry KW - Monte-Carlo simulations KW - Radiation damage KW - Radiation therapy KW - SEM KW - Electron Microscope KW - LEE KW - Protein PY - 2018 AN - OPUS4-46383 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - Irradiation of biomolecules in liquid with electrons of different linear energy transfer N2 - The damage caused by ionizing radiation to DNA and proteins is the reason to treat cancer by radiation therapy. A better understanding of the molecular processes and quantification of the different damaging mechanisms is the prerequisite to develop more efficient therapies. Hereby the understanding of the processes involved in the damage to DNA are of key interest due to its central role in reproduction and mutation. For radiation with low linear energy transfer (LET), most of the damage is caused by the secondary particles produced by scattering of the ionizing radiation with water. Thereby a multitude of species are produced, whereby especially kinetic low energy electrons, prehydrated electrons, OH-radicals and ions are of importance. With higher LET the relative amount of the direct damaging effects increases. This is especially important considering the increased usage of high LET particles in radiation therapy. Therefore, the quantification of the contribution to DNA damage of direct and indirect effects and the different secondary species is of high interest due to the increase of radio biological efficiency when applying high LET radiation. Here we present an approach to investigate the relative contributions to DNA strand break yield for radiation of different LET within a single electron microscope in combination with electron scattering simulations. T2 - International workshop on radiation damage to DNA CY - Aussois, France DA - 27.05.2018 KW - Radiation damage KW - LET KW - Geant4 KW - DNA KW - Radiation therapy KW - Hydroxyl radical KW - Low energy electrons KW - Dosimetry KW - Microdosimetry KW - Electron irradiation KW - Sem KW - Linear energy transfer KW - MCS KW - Monte-Carlo simulations PY - 2018 AN - OPUS4-45103 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - DNA strand break yields by OH-radicals, low energy electrons and prehydrated electrons N2 - Universität Berlin Radiation damage to biomolecules such as DNA, is the reason to treat cancer via radiation therapy. The understanding of the molecular processes and the quantification of the underlying damaging mechanisms is necessary to develope more efficient irradiation protocols for cancer therapy. Thereby damage to DNA is of key interest due to its central role in reproduction and mutation. Due to the high amount of water in biological tissue, most of the damage is caused by the secondary particles which are produced by the interaction of ionizing radiation with water. Thereby a multitude of species are produced, e.g. kinetic low energy electrons, prehydrated electrons, OH-radicals and ions. The quantification of the contribution to DNA damage by the various species is of interest. Here we present an experimental approach to disentangle their relative DNA strand break yields. Plasmid DNA (pUC19 ) is irradiated in water with electrons under the presence of different scavengers. The presented preliminary results reveal the relative contributions of OH-radicals, low energy electrons and prehydrated electrons and their DNA single and double strand break yields. T2 - DPG-Frühjahrstagung der Sektion Kondensierte Materie gemeinsam mit der EPS CY - Berlin, Germany DA - 11.03.2018 KW - DNA KW - Radiation damage KW - Dosimetry KW - Low energy electrons KW - Hydroxyl radicals KW - Geant4 KW - Prehydrated electrons KW - Scavenger KW - Radiation damage to DNA KW - Plasmid DNA KW - Strand breaks KW - Double strand breaks KW - Single strand breaks PY - 2018 AN - OPUS4-44566 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - Combination of Monte-Carlo simulations and experimental results to determine the microscopic energy depoit at DNA N2 - The quantification of radiation induced damage to DNA in aqueous en- vironment is of fundamental interest for dosimetry and its application in radiation-therapy and protection. We present a combined experi- mental and simulational approach to quantify and compare radiation induced damage to biomolecules in liquid environment for a wide range of primary radiation sources e. g. photons, electrons or ions and tar- gets, such as DNA, proteins or cells.[1] To show its viability, we will apply this method to an experimentally challenging systems, the di- rect irradiation of plasmid DNA (pUC19) in water with electrons as primary particles. Here we combine Geant4 electron-scattering simula- tions with calculations concerning the diffusion and convection induced movement of the biomolecules, within a coarse-grained model of the irradiated liquid. Additionally a microscopic target model for the plas- mid DNA based on the relation of lineal energy and radiation quality is used to calculate the effective target volume. T2 - DPG-Frühjahrstagung der Sektion Kondensierte Materie gemeinsam mit der EPS CY - Berlin, Germany DA - 11.03.2018 KW - DNA KW - Radiation damage KW - Dosimetry KW - Microdosimetry KW - Low energy electrons KW - Hydroxyl radicals KW - Monte-Carlo simulation KW - Geant4 KW - Electron scattering KW - Target volume KW - DNA damage KW - DNA radiation damage PY - 2018 AN - OPUS4-44565 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - A standard procedure for the irradiation of biomolecules with radiation of varying linear energy transfer N2 - The damage caused by ionizing radiation to DNA and proteins is the reason to treat cancer by radiation therapy. A better understanding of the molecular processes and quantification of the different damaging mechanisms is the prerequisite to develop more efficient therapies. Hereby the understanding of the processes involved in the damage to DNA are of key interest due to its central role in reproduction and mutation. For radiation with low linear energy transfer (LET), most of the damage is caused by the secondary particles produced by scattering of the ionizing radiation with water. Thereby a multitude of species are produced, whereby especially kinetic low energy electrons, prehydrated electrons, OH-radicals and ions are of importance. With higher LET the relative amount of the direct damaging effects increases. This is especially important considering the increased usage of high LET nucleons in radiation therapy. Therefore, the quantification of the contribution to DNA damage of direct and indirect effects and the different secondary species is of high interest due to the increase of radio biological efficiency when applying high LET radiation. Here we present an approach to investigate the relative contributions to DNA strand break yield for radiation of different LET within a single electron microscope in combination with electron scattering simulations. T2 - IRPA 2018 CY - Havanna, Cuba DA - 16.04.2018 KW - Dosimetry KW - Microdosimetry KW - LET KW - SEM KW - DNA KW - Radiation damage KW - OH radicals KW - LEE KW - Ionizing radiation KW - Geant4 PY - 2018 AN - OPUS4-44820 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Kunte, Hans-Jörg A1 - Meyer, Susann A1 - Schröter, Maria-Astrid A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - Ectoine protects biomolecules from ionizing radiation: Molecular mechanisms N2 - The compatible solute and osmolyte ectoine is an effective protectant of biomolecules and whole cells against heating, freezing and high salinity. The protection of cells (human Keratinocytes) by ectoine against ultraviolet radiation was also reported by various authors, although the underlying mechanism is not yet understood. We present results on the irradiation of biomolecules (DNA) with ionizing radiation (high energy electrons) in fully aqueous environment in the presence of ectoine and high salt concentrations. The results demonstrate an effective radiation protection of DNA by ectoine against the induction of single strand breaks by ionizing radiation. The effect is explained by an increased in low-energy electron scattering at the enhanced free-vibrational density of states of water due to ectoine, as well as the action of ectoine as an OH-radical scavenger. This was demonstrated by Raman spectroscopy, electron paramagnetic resonance (EPR) and Monte-Carlo simulations (Geant4). T2 - DPG-Frühjahrstagung der Sektion Kondensierte Materie gemeinsam mit der EPS CY - Berlin, Germany DA - 11.03.2018 KW - Ionizing radiation KW - Ectoine KW - Radiation damage KW - Radiation protection KW - Dosimetry KW - Ectoin KW - Ectoine radiation protection KW - Compatible solute KW - Osmolyte KW - Aqueous solution KW - OH-radical KW - Radical scavenger KW - Hydroxyl radical KW - Hydroxyectoine KW - Ectoine radical scavenger KW - Low energy electrons KW - Geant4 PY - 2018 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-446202 N1 - Poster basiert auf: https://nbn-resolving.org/urn:nbn:de:kobv:b43-419332 AN - OPUS4-44620 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Geant4: A universal Monte-Carlo toolkit for Particle scattering simulations N2 - Particle scattering simulations are an useful tool to plan experiments, design detectors, estimate doses in irradiated materials and medical treatment planning. Geant4 is a Monte-Carlo toolkit for the simulation of of particles scattering in matter. Photons, electrons, ions etc can be simulated with energies in the eV to GeV range. Their interactions with matter in arbitrary scattering geometries be studied. Scattering models, cross sections and material parameters can be set to cover interactions in gas, liquid and solid state. The import of geometries from computer aided design files or the protein data base is possible. It is currently being applied in high energy and nuclear physics, accelerator and detector design, space application, dosimetry and medical sciences. In this first part of the talk a brief overview over the structure, functionality and possible applications of Geant4 will be given. In the second part an example application will be presented: The determination of the microscopic dose-damage relations in aqueous environment for electron irradiated plasmid DNA will be explained. Therefore, we combine electron scattering simulations in water with calculations concerning the movement of biomolecules to obtain the energy deposit in the biologically relevant nanoscopic volume. We present, how to combine these simulational results and experimental data via a generalized damage model to determine the microscopic dose-damage relation at a molecular level. T2 - Department 6 Seminar CY - Berlin, Germany DA - 04.04.2019 KW - Geant4 KW - Dosimetry KW - Microdosimetry KW - Radiation damage KW - Electron irradiation KW - Monte-Carlo Simulation KW - Monte-Carlo Simulations KW - DNA KW - Computer simulation KW - Geant4-DNA PY - 2019 AN - OPUS4-47819 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - Measurement and Simulation of the Microscopic Energy Deposit: A general approach applicable to Ionizing Radiation Sources of varying Linear Energy Transfer N2 - The determination of microscopic dose-damage relations in aqueous environment is of fundamental interest for dosimetry and its application in radiation-therapy and protection. We present a combined experimental and simulational approach to quantify the microscopic energy deposit at biomolecules in liquid environment which is applicable to a wide range of primary radiation sources, e.g. photons, electrons or ions, and targets, such as DNA, proteins or cells.Therefore, we combine Geant4 particle-scattering simulations in water with calculations concerning the movement of biomolecules to obtain the energy deposit in the biologically relevant nanoscopic volume. We present, how to combine these simulational results and experimental data via a generalised damage model to determine the microscopic dose-damage relation at a molecular level. To show the viability of this approach, we apply this method to an experimentally challenging system, the direct irradiation of plasmid DNA (pUC19) in water with electrons as primary particles. Here we combine electron-scattering simulations with calculations concerning the diffusion and convection induced movement of the DNA, within a coarse-grained model of the irradiated liquid. Additionally a microscopic target model for DNA molecules based on the relation of lineal energy and radiation quality is used to calculate their effective target volume. It was found that on average fewer than two ionisations within a 7.5\,nm radius around the sugar-phosphate backbone are sufficient to cause a single strand break, with a corresponding median lethal energy deposit being E\textsubscript{1/2}=6+-4\,eV. The presented method is applicable for all types of ionising radiation and a broad variety of biological targets. T2 - CCQM Workshop CY - Paris, France DA - 09.04.2019 KW - Dosimetry KW - Microdosimetry KW - Geant4 KW - Geant4-DNA KW - DNA KW - Electron irradiation KW - Monte-Carlo Simulation PY - 2019 UR - https://www.bipm.org/utils/en/pdf/Workshop-CCQM2019-EP1.pdf AN - OPUS4-47810 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hahn, Marc Benjamin A1 - Zutta Villate, Julian Mateo T1 - Radioactive gold nanoparticles for cancer treatment: Size and cluster dependent damage studied by Geant4 Monte-Carlo simulations N2 - Dose enhancement by gold nanoparticles (AuNP) was shown to increase the biological effectiveness of radiation damage in biomolecules and tissue. Most of the current studies focus on external beam therapy on combination with AuNP. Here we present a Monte-Carlo study (Geant4) to characterise radioactive AuNP. Radioactive ¹⁹⁸Au emits beta and gamma rays and is considered for applications with solid tumours. To effectively apply ¹⁹⁸AuNP their energy deposit characteristics have to be determined in terms of intrinsic and extrinsic properties e.g. AuNP diameter, AuNP density, and their clustering behaviour. After each decay process, the energy deposit, inelastic scattering events, kinetic energy spectrum of secondary particles within the AuNP themselves and in a spherical target volume of water up to 1 μm radius were determined. Simulations were performed for AuNP radii ranging from 2.5 nm to 20 nm radius, different cluster sizes and densities. The results show an increase of the energy deposit in the vicinity of the AuNP up to 150 nm. This effect nearly vanishes for distances up to one micron. For the case of AuNP clusters and the same activity, the enhancement of the energy deposit increases with the relative gold mass percentage and therefore can be adjusted by changing AuNP radius or clustering behaviour. KW - Gold Nanoparticles KW - AuNP KW - Radioactive decay KW - Beta decay KW - DNA KW - DNA damage KW - Radiation damage KW - MCS KW - Monte-Carlo simulation KW - Geant4 KW - Dosimetry KW - Microdosimetry KW - Cancer treatment KW - Radiationtherapy KW - Brachytherapy KW - OH radicals KW - LEE KW - low energy electrons KW - gamma ray KW - beta particle KW - radiolysis KW - clustered nanoparticles KW - NP KW - Simulation KW - particle scattering KW - Geant4-DNA KW - Energy deposit PY - 2019 DO - https://doi.org/10.1140/epjd/e2019-90707-x SN - 1434-6060 SN - 1434-6079 VL - 73 IS - 5 SP - 95, 1 EP - 7 PB - Springer CY - Berlin Heidelberg AN - OPUS4-47952 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Simulational tools in nanoparticle research: Micromagnetics and particle scattering N2 - Simulational tools are applied to investigate the physical properties of nanoparticles. For the description of radioactive gold nanoparticles, particles scattering simulations are performed with the Geant4 monte carlo simulation toolkit. The temperature dependent behaviour of the magnetization dynamics of different magnetic nanoparticles are simulated with the object oriented micormagnetic framework (OOMMF). T2 - NanoBioAp CY - LLanes, Spain DA - 23.05.2019 KW - Monte Carlo KW - Monte-Carlo simulation KW - MCS KW - Nanoparticle KW - AuNP KW - Dosimetry KW - Radioactive NP KW - Microdosimetry KW - Geant4 KW - OOMMF KW - Micromagnetism KW - Simulation KW - Magnetic nanoparticle KW - LLG PY - 2019 AN - OPUS4-48110 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Zutta Villate, J. M. T1 - Radioactive gold nanoparticles for cancer treatment: Size and cluster dependent damage studied by Geant4 Monte-Carlo simulations N2 - Dose enhancement by gold nanoparticles (AuNP) was shown to increase the biological effectiveness of radiation damage in biomolecules and tissue. Most of the current studies focus on external beam therapy on combination with AuNP. Here we present a Monte-Carlo study (Geant4) to characterise radioactive AuNP. Radioactive ¹⁹⁸Au emits beta and gamma rays and is considered for applications with solid tumours. To effectively apply ¹⁹⁸AuNP their energy deposit characteristics have to be determined in terms of intrinsic and extrinsic properties e.g. AuNP diameter, AuNP density, and their clustering behaviour. After each decay process, the energy deposit, inelastic scattering events, kinetic energy spectrum of secondary particles within the AuNP themselves and in a spherical target volume of water up to 1 μm radius were determined. Simulations were performed for AuNP radii ranging from 2.5 nm to 20 nm radius, different cluster sizes and densities. The results show an increase of the energy deposit in the vicinity of the AuNP up to 150 nm. This effect nearly vanishes for distances up to one micron. For the case of AuNP clusters and the same activity, the enhancement of the energy deposit increases with the relative gold mass percentage and therefore can be adjusted by changing AuNP radius or clustering behaviour. T2 - EUROMAT 2019 CY - Stockholm, Sweden DA - 01.09.2019 KW - DNA KW - Dosimetry KW - Microdosimetry KW - Geant4 KW - MCS KW - Nanoparticle KW - AuNP KW - Gold Nanoparticle KW - low energy electrons KW - LEE KW - OH radicals KW - particle scattering KW - Radiationtherapy KW - Radioactive decay KW - Monte-Carlo simulation KW - Energy deposit KW - DNA damage PY - 2019 AN - OPUS4-48763 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - DNA basierte Dosimetrie N2 - We propose the development of a standardized DNA based dosimeter. This dosimeter will improve the comparability between the results of different laboratories in radiation research. Compared to conventional methods in dosimetry, this Approach provides direct access to the relation between radiation interaction and biological damage. Moreover, it enables the systematic investigation of the relation between the microscopic characteristics of radiation and DNA damage over a wide dose range. T2 - Zertkom CY - Online meeting DA - 13.05.2020 KW - DNA KW - Dosimetrie KW - Dosimetry KW - Effective dose KW - Energy dose KW - Energiedosis KW - Equivalent dose KW - Absorbed dose PY - 2020 AN - OPUS4-50779 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Hahn, Marc Benjamin T1 - TOPAS cell model with nanoparticles N2 - These files contain cell models for TOPAS/Geant4 and the inclusion of nano particles in particle scattering simulations. A simple spherical cell with nanoparticles can be generated in a fast manner. The user has the option to include the following organelles: nucleus, mitochondria, cell membrane. Additionally nanoparticles can be included in the cytosol and at the surface of the nucleus and/or the mitochondria. The C++ classes in this repository extend the functionality of the TOPAS (http://www.topasmc.org/) Monte-Carlo program, which is itself a wrapper of the Geant4 MCS Toolkit (http://geant4.org). The sourcecode together with examples and scorers are provided. "If you use this extension please cite the following literature: Hahn, M.B., Zutta Villate, J.M. "Combined cell and nanoparticle models for TOPAS to study radiation dose enhancement in cell organelles." Sci Rep 11, 6721 (2021). https://doi.org/10.1038/s41598-021-85964-2 " KW - Monte-Carlo simulation KW - MCS KW - Geant4 KW - TOPAS KW - TOPAS-nBio KW - Dosimetry KW - Nanoparticles KW - Nanoparticle KW - AuNP KW - Gold KW - Microdosimetry KW - Targeted nanoparticle KW - Simulation KW - Particle scattering KW - Cell KW - Nucleus KW - Mitochondria KW - Cancer therapy KW - Radiation therapy PY - 2020 UR - https://github.com/BAMresearch/TOPAS-CellModels UR - https://github.com/MarcBHahn/TOPAS-CellModels DO - https://doi.org/10.26272/opus4-51150 PB - Bundesanstalt für Materialforschung und -prüfung (BAM) CY - Berlin AN - OPUS4-51150 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Particle Scattering Simulations with Geant4: An Overview N2 - A brief overview over the capabilities of Geant4 is provided together with some example applications T2 - Seminar of the bioanalysis group CY - Universidad Nacional de Colombia, Bogotá, Columbia DA - 03.02.2020 KW - Geant4 KW - Geant4-DNA KW - MCS KW - Simulation KW - Monte-Carlo simulation KW - Particle scattering simulation KW - Dosimetry KW - Xrays KW - Electrons KW - Radiation PY - 2020 AN - OPUS4-50332 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - DNA based Reference Materials: In Biodosimetry and Pharmaceutical Quality Control N2 - Applications of plasmid DNA base reference materials in dosimetry and pharmaceutical research. T2 - Physical and Chemical Analysis of Polymers seminar CY - Online meeting DA - 29.03.2021 KW - Analytic KW - Certification KW - DNA KW - Dosimetry KW - Homogeneity KW - Quality testing KW - Reference material KW - Referenzmaterialien KW - Stability KW - Dose KW - Radiation KW - Pharmacy KW - Electrohpresis PY - 2021 AN - OPUS4-52361 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - RPRT A1 - Hahn, Marc Benjamin A1 - Sturm, Heinz A1 - Bier, F A1 - Solomun, Tihomir T1 - Biologische Konsequenzen einer nanoskaligen Energiedeposition: Fokussierung auf die Rolle niederenergetischer Elektronen T1 - Biological Consequence of Nanoscale Energy Deposition: Focusing on the Role of Low-Energy Electrons N2 - Bei der Behandlung von Krebs mittels Strahlentherapie sollen Tumorzellen abgetötet werden ohne das umliegende gesunde Gewebe zu zerstören. Um Strahlentherapien für Patienten verträglicher zu machen, ist ein besseres Verständnis der zugrundeliegenden Prozesse auf der molekularen Ebene nötig. Dabei sind der Energieeintrag und die Streuprozesse der Strahlung in der Umgebung der DNA von besonderem Interesse. Durch Streuung von hochenergetischer Strahlung in Wasser werden besonders viele Sekundärelektronen mit niedriger Energie erzeugt. Zur Untersuchung der Schädigungseffizienz dieser Elektronen wurde ein Verfahren zur direkten Bestrahlung von Lösungen mittels Elektronen variabler Energien enwtickelt. Dies wurde durch einen neu entwickelten Probenhalter mit einer für Elektronen durchlässigen Nanomembran ermöglicht. Mit diesem können Bestrahlungen an DNA, Proteinen, und Zellen bei verschiedenen pH-Werten oder Salzkonzentrationen durchgeführt werden. Parallel dazu wurde der ortsabhängige Energieeintrag innerhalb des Wassers durch Elektronenstreusimulationen bestimmt. Diese neuartige Kombination von Experiment und Simulation ermöglicht die Bestimmung der Schaden-Dosis-Relation für Elektronenbestrahlung von biologischen Systemen unter realistischen physiologischen Bedingungen. So konnten für die genutzten Primärelektronen wie die mittlere letale Dosis, bei der 50 Prozent der DNA geschädigt sind, mit 1,7 Gy bestimmt. Ebenfalls wurde das für mikrodosimetrische Modellierungen und Betrachtungen der sogenannten Linear energy transfer (LET) Effekte, wichtige Verhältnis von DNA Einzelstrangbrüchen (SSB) zu Doppelstrangbrüchen (DSB) als SSB/DSB = 12/1 bestimmt. Mit Hilfe eines Modells für das Targetvolumen der DNA wurde 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. Diese Methode ist unabhängig von den Primärpartikel und geometrischen Bedingungen. Deshalb ermöglicht sie die Vergleichbarkeit experimenteller Systeme mit inhomogenen Energieverteilungen, welches sonst nicht gegeben ist. Des weiteren wurden die Strahlenschutzfunktionen des Zellschutzmoleküls Ectoines und sein Einfluss auf Wasser und Biomoleküle untersucht. Seine Schutzfunktion gegen ionisierende Strahlung wurde auf die Erhöhung des Streuquerschnitts niederenergetischer Elektronen und seine Eigenschaft als OH-Radikalfänger zurückgeführt. Aufbauend auf unseren Erkenntnissen finden in klinischen Arbeitsgruppen Untersuchungen zu Einsatzmöglichkeiten im Umfeld der Strahlentherapie statt. Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 245767821 N2 - To cure cancer radiation therapy is used to kill tumor cells. It is based on radiation induced damage to biomolecules. Here 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 the-rapies. Therefore irradiations have to be performed in liquid, under consideration of the chemical environment. 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 and salinity. 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 is 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 was investigated. 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. Based on our results, further investigations are conducted to evaluate the application of Ectoine in the context of radiation therapy. Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 245767821 KW - Ectoin KW - Ectoine KW - DNS KW - DNA KW - Cancer therapy KW - DNA damage KW - DNA radiation damage KW - Dosimetry KW - DFG KW - Electron irradiation KW - Ectoine DNA interaction KW - Ectoine radiation protection KW - Hydroxyl radicals KW - OH radicals KW - LEE KW - Low energy electrons KW - Microdosimetry KW - Radiation KW - Geant4 KW - Geant4-DNA KW - Radiation therapy KW - LET PY - 2021 UR - https://gepris.dfg.de/gepris/projekt/245767821/ergebnisse?context=projekt&task=showDetail&id=245767821&selectedSubTab=2& SP - 1 EP - 14 AN - OPUS4-52389 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 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 - Radnik, Jörg A1 - Dietrich, P. M. T1 - Near-Ambient-Pressure XPS to investigate radiation damage to DNA 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. T2 - Physical and Chemical Analysis of Polymers seminar CY - Online meeting DA - 12.10.2021 KW - Base damage KW - Base loss KW - Cancer therapy KW - DNA KW - DNA radiation damage KW - Direct damage KW - Dissociative electron attachment (DEA) KW - Dissociative electron transfer (DET) KW - Dosimetry KW - Double-strand break KW - DSB KW - Dry DNA KW - Geant4 KW - Geant4-DNA KW - Hydrated DNA KW - Hydrated electron KW - Hydration shell KW - Hydroxyl radical KW - Indirect damage KW - Ionization KW - LEE KW - Low energy electrons 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 - ROS KW - Radiation damage KW - Radiation therapy KW - Radical KW - Reactive oxygen species KW - Single-strand break KW - SSB KW - TOPAS KW - TOPAS-nbio KW - XPS KW - Xray KW - Xray photo electron spectrocopy PY - 2021 AN - OPUS4-53611 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Reference Materials at BAM N2 - A introduction into reference materials, the certification process and brief over current reference projects at BAM is given. T2 - AK-Postdoc seminar CY - BAM Berlin, Germany DA - 02.02.2021 KW - Referenzmaterialien KW - Reference material KW - Homogeneity KW - Stability KW - Quality testing KW - Analytic KW - DNA KW - Dosimetry KW - Certification PY - 2021 AN - OPUS4-52060 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 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 - Zutta Villate, J. M. T1 - Combined cell and nanoparticle models for TOPAS to study radiation dose enhancement by Monte-Carlo based particle scattering Simulations 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.[1] 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. [2] 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 ongoing experimental work which aims to obtain a mechanistic understanding of cell death induced by radioactive 198Au. T2 - NALS 2022 CY - Santander, Spain DA - 27.04.2022 KW - AuNP KW - Beta decay KW - beta particle KW - Brachytherapy KW - Cancer treatment KW - Clustered nanoparticles KW - DNA KW - DNA damage KW - Dosimetry KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Gold Nanoparticles KW - LEE KW - Livermore model KW - Low energy electrons KW - MCS KW - Microdosimetry KW - Monte-Carlo simulation KW - NP KW - OH radical KW - particle scattering KW - Penelope model KW - Radiation damage KW - Radiation therapy KW - Radiationtherapy KW - Radioactive decay KW - Radiolysis KW - Simulation KW - TOPAS KW - TOPAS-nbio PY - 2022 AN - OPUS4-54775 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Zutta Villate, J. M. A1 - Viviana Rojas, J. A1 - Hahn, Marc Benjamin A1 - Anselmo Puerta, J. T1 - Synthesis of 198Au nanoparticles sub 10 nm due optimization on local dose by Monte Carlo simulations for cancer treatment N2 - To enhance the biological effects of radiation damage in cancerous cells, we present an alternative approach to the use of gold nanoparticles (AuNP), focusing on the synthesis and characterization of highly monodisperse, spherical radioactive gold nanoparticles 198AuNP. The size of the AuNP size was optimized with the help of Geant4/TOPAS particle scattering simulations, and energy deposition per nm3 per decay for varying radii (2–10 nm) was evaluated. This work is the foundation for ongoing experimental work to evaluate cell death induced by 198AuNP which aims for the use of radioactive gold nanoparticles in cancer treatment. KW - AuNP KW - Beta decay KW - Beta particle KW - Brachytherapy KW - Cancer treatment KW - Nanoparticles KW - Nanoparticle KW - DNA KW - DNA damage KW - Dosimetry KW - Energy deposit KW - Gamma ray KW - Geant4 KW - Geant4-DNA KW - Gold Nanoparticles KW - LEE KW - Low energy electrons KW - MCS KW - Microdosimetry KW - Monte-Carlo simulation KW - NP KW - Synthesis KW - TEM KW - OH radicals KW - Particle scattering KW - Radiation damage KW - Radiationtherapy KW - Radioactive decay KW - Radiolysis KW - Simulation KW - TOPAS KW - TOPAS-nbio PY - 2022 DO - https://doi.org/10.1007/s10967-022-08355-5 SN - 1588-2780 SP - 1 EP - 9 PB - Springer Nature AN - OPUS4-55132 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Hahn, Marc Benjamin T1 - BioSAXS models for TOPAS/Geant4 N2 - Models for TOPAS/Geant4 to estimate the microscopic dose received by biomolecules during bioSAXS experiments. The C++ classes in this repository extend the functionality of the TOPAS (http://www.topasmc.org/) Monte-Carlo program, which is itself a wrapper of the Geant4 MCS Toolkit (http://geant4.org). KW - TOPAS KW - TOPAS-nBio KW - Geant4 KW - Geant4-DNA KW - MCS KW - Microdosimetry KW - Protein KW - Proteins KW - Particle scattering KW - G5P KW - GV5 KW - SAXS KW - Monte-Carlo simulation KW - Dosimetry KW - Micorscopic dose-damage relation PY - 2022 UR - https://github.com/MarcBHahn/TOPAS-bioSAXS-dosimetry DO - https://doi.org/10.26272/opus4-55751 PB - Bundesanstalt für Materialforschung und -prüfung (BAM) CY - Berlin AN - OPUS4-55751 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 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 A1 - Hallier, Dorothea C. A1 - Dietrich, P. M. A1 - Radnik, Jörg T1 - In-situ monitoring of water dependent DNA and protein radiation damage 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. T2 - ICRR 2023 CY - Montreal, Canada DA - 26.08.2023 KW - DNA KW - XPS KW - Proteins KW - Protein KW - G5P KW - Base damage KW - Base loss KW - Cancer treatment KW - DEA KW - DET KW - DNA radiation damage KW - Direct damage KW - Dissociative electron attachment (DEA) KW - Dissociative electron transfer (DET) KW - Dosimetry KW - ESCA KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Hydrated DNA KW - Hydrated electron KW - Hydrated electrons KW - Hydration shell KW - Hydroxyl radical KW - Indirect damage KW - Ionisation KW - Ionization KW - LEE KW - Low energy electrons KW - MCS KW - Microdosimetry KW - NAP-XPS KW - Near ambient pressure xray photo electron spectroscopy KW - Net-ionization reaction KW - OH radical KW - PES KW - Particle scattering KW - Prehydrated electron KW - Presolvated electron KW - Quasi-direct damage KW - ROS KW - Radiation damage KW - Radiation therapy KW - Radical KW - Radiolysis KW - Radiotherapy KW - Reactive oxygen species KW - Simulation KW - Single-strand break (SSB) KW - Single-stranded DNA-binding proteins KW - TOPAS KW - TOPAS-nbio KW - TopasMC KW - Xray photo electron spectrocopy PY - 2023 AN - OPUS4-58214 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" 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 - CONF A1 - Hahn, Marc Benjamin A1 - Dietrich, Paul M. A1 - Radnik, Jörg 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. T2 - Dyson Conference 2023 CY - Prague, Czech Republic DA - 24.04.2023 KW - Base damage KW - Base loss KW - Cancer treatment KW - DNA KW - DNA radiation damage KW - Direct damage KW - Dissociative electron attachment (DEA) KW - Dissociative electron transfer (DET) KW - Dosimetry KW - Double-strand break (DSB) KW - ESCA KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Hydrated DNA KW - Hydrated electron KW - Hydration shell KW - Hydroxyl radical KW - Indirect damage KW - Ionization KW - Ionisation KW - LEE KW - Low energy electrons KW - MCS KW - Microdosimetry KW - NAP-XPS KW - Near ambient pressure xray photo electron spectroscopy KW - Net-ionization reaction KW - OH radical KW - PES KW - Particle scattering KW - Prehydrated electron KW - Presolvated electron KW - Quasi-direct damage KW - ROS KW - Radiation damage KW - Radiation therapy KW - Radical KW - Radiolysis KW - Radiotherapy KW - Reactive oxygen species KW - Simulation KW - Single-strand break (SSB) KW - TOPAS KW - TOPAS-nbio KW - XPS KW - Xray KW - Xray photo electron spectrocopy KW - G5P KW - Protein KW - Single-stranded DNA-binding proteins PY - 2023 AN - OPUS4-57406 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 - Hahn, Marc Benjamin T1 - Accessing radiation damage to biomolecules on the nanoscale by particle-scattering simulations N2 - Radiation damage to DNA plays a central role in radiation therapy to cure cancer. The physico-chemical and biological processes involved encompass huge time and spatial scales. To obtain a comprehensive understanding on the nano and the macro scale is a very challenging tasks for experimental techniques alone. Therefore particle-scattering simulations are often applied to complement measurements and aide their interpretation, to help in the planning of experiments, to predict their outcome and to test damage models. In the last years, powerful multipurpose particle-scattering framework based on the Monte-Carlo simulation (MCS) method, such as Geant4 and Geant4-DNA, were extended by user friendly interfaces such as TOPAS and TOPAS-nBio. This shifts their applicability from the realm of dedicated specialists to a broader range of scientists. In the present review we aim to give an overview over MCS based approaches to understand radiation interaction on a broad scale, ranging from cancerous tissue, cells and their organelles including the nucleus, mitochondria and membranes, over radiosensitizer such as metallic nanoparticles, and water with additional radical scavenger, down to isolated biomolecules in the form of DNA, RNA, proteins and DNA-protein complexes. Hereby the degradation of biomolecules by direct damage from inelastic scattering processes during the physical stage, and the indirect damage caused by radicals during the chemical stage as well as some parts of the early biological response is covered. Due to their high abundance the action of hydroxyl radicals (•OH) and secondary low energy electrons (LEE) as well as prehydrated electrons are covered in additional detail. Applications in the prediction of DNA damage, DNA repair processes, cell survival and apoptosis, influence of radiosensitizer on the dose distribution within cells and their organelles, the study of linear energy transfer (LET), the relative biological effectiveness (RBE), ion beam cancer therapy, microbeam radiation therapy (MRT), the FLASH effect, and the radiation induced bystander effect are reviewed. KW - DNA KW - Protein KW - G5P KW - OH KW - Au KW - AuNP KW - Radiation KW - SSB KW - DSB KW - Beta decay KW - Brachytherapy KW - Cancer treatment KW - Clustered nanoparticles KW - DNA damage KW - Dosimetry KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Gold Nanoparticles KW - Livermore model KW - Low energy electrons KW - MCS KW - Microdosimetry KW - Monte-Carlo simulation KW - NP KW - OH radical KW - Particle scattering KW - Penelope model KW - Proteins KW - Radiation damage KW - Radiation therapy KW - Radiationtherapy KW - Radioactive decay KW - Radiolysis KW - Radiotherapy KW - Simulation KW - TOPAS KW - TOPAS-nbio KW - Base damage KW - Base loss KW - DNA radiation damage KW - Direct damage KW - Dissociative electron attachment (DEA) KW - Dissociative electron transfer (DET) KW - Double-strand break (DSB) KW - ESCA KW - Hydrated DNA KW - Hydrated electron KW - Hydration shell KW - Hydroxyl radical KW - Indirect damage KW - Ionization KW - Ionisation KW - NAP-XPS KW - Near ambient pressure xray photo electron spectroscopy KW - Net-ionization reaction KW - Prehydrated electron KW - Presolvated electron KW - Quasi-direct damage KW - ROS KW - Radical KW - Reactive oxygen species KW - Single-strand break (SSB) KW - XPS KW - Xray KW - Xray photo electron spectrocopy KW - Cosolute KW - Ectoin KW - Ectoine KW - GVP KW - Gene five protein KW - Hydroxyectoine KW - Ionizing radiation damage KW - OH radical scavenger KW - Monte-Carlo simulations KW - Nanodosimetry KW - Osmolyte KW - Particle scattering simulations KW - Protein unfolding KW - Radical Scavenge KW - Radical scavenger KW - Single-stranded DNA-binding proteins KW - SAXS KW - Bio-SAXS KW - X-ray scattering KW - ssDNA KW - dsDNA KW - FLASH effect KW - Bystander effect KW - Ion beam therapy KW - Bragg peak KW - LET KW - MCNP KW - Photons KW - Electrons KW - Carbon ions KW - MRT KW - RNA KW - RBE KW - base loss KW - abasic side KW - DMSO KW - Cells PY - 2023 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-573240 DO - https://doi.org/10.1088/2399-6528/accb3f SN - 2399-6528 VL - 7 IS - 4 SP - 042001 PB - Institute of Physics (IOP) Publishing CY - London AN - OPUS4-57324 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Zutta Villate, J. M. T1 - BP150: Combined cell and nanoparticle models for TOPAS to study radiation dose enhancement by Monte-Carlo based particle scattering Simulations 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. In this work, two newly developed continuous and discrete-geometric models for simulations of AuNP in cells are presented. 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. T2 - DPG Frühjahrstagung CY - Dresden, Germany DA - 26.03.2023 KW - AuNP KW - Beta decay KW - Brachytherapy KW - Cancer treatment KW - Clustered nanoparticles KW - DNA KW - DNA damage KW - Dosimetry KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Gold Nanoparticles KW - LEE KW - Livermore model KW - Low energy electrons KW - MCS KW - Microdosimetry KW - Monte-Carlo simulation KW - NP KW - OH radical KW - Penelope model KW - Radiation damage KW - Radiation therapy KW - Radiationtherapy KW - Radioactive decay KW - Radiolysis KW - Radiotherapy KW - Simulation KW - TOPAS KW - TOPAS-nbio KW - Beta particle KW - Particle scattering KW - Protein KW - Proteins PY - 2023 AN - OPUS4-57253 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 - BP150: Bio-SAXS of single-stranded DNA-binding proteins: Radiation protection by the compatible solute ectoine N2 - Small-angle X-ray scattering (SAXS) can be used for structural determination of biological macromolecules and polymers in their native states (e.g. liquid phase). This means that the structural changes of (bio-)polymers, such as proteins and DNA, can be monitored in situ to understand their sensitivity to changes in chemical environments. In an attempt to improve the reliability of such experiments, the reduction of radiation damage occurring from exposure to X-rays is required. One such method, is to use scavenger molecules to protect macromolecules against radicals produced during radiation exposure, such as reactive oxygen species (ROS). In this study we investigate the feasibility of applying the compatible solute, osmolyte and radiation protector Ectoine (THP(B)), as a scavenger molecule during SAXS measurements of the single-stranded DNA-binding protein Gene-V Protein (G5P/GVP). In this case, we monitor the radiation induced changes of G5P during bio-SAXS measurments and the resulting microscopic energy-damage relation was determined from microdosimetric calculations by Monte-Carlo based particle scattering simulations with TOPAS/Geant4 and a custom target-model. This resulted in a median-lethal energy deposit of pure G5P at 4 mg mL−1 of E1/2 = 7 ± 5 eV, whereas a threefold increase of energy-deposit was needed under the presence of Ectoine to reach the same level of damage. This indicates that Ectoine increases the possible exposure time before radiation-damage to G5P is observed. Furthermore, the dominant type of damage shifted from aggregation in pure solutions towards a fragmentation for solutions containing Ectoine as a cosolute. These results are interpreted in terms of indirect radiation damage by reactive secondary species, as well as post-irradiation effects, related to preferential-exclusion of the cosolute from the protein surface. Hence, Ectoine is shown to provide a non-disturbing way to improve structure-determination of proteins via bio-SAXS in future studies. T2 - DPG Frühjahrstagung CY - Dresden, Germany DA - 26.03.2023 KW - Bio-SAXS KW - BioSAXS KW - Compatible solute KW - Cosolute KW - DNA KW - Dosimetry KW - Ectoin KW - Ectoine KW - G5P KW - GVP KW - Gene five protein KW - Geant4 KW - Geant4-DNA 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 - Proteins KW - Protein unfolding KW - ROS KW - Radiation damage 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 - Radical scavenger KW - ssDNA PY - 2023 AN - OPUS4-57254 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 - BP153: The change of DNA radiation damage upon hydration: In-situ observation 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 - DPG Frühjahrstagung CY - Dresden, Germany DA - 26.03.2023 KW - Base damage KW - Base loss KW - Cancer treatment KW - DNA KW - DNA radiation damage KW - Direct damage KW - Dissociative electron attachment (DEA) KW - Dissociative electron transfer (DET) KW - Dosimetry KW - Double-strand break (DSB) KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Hydrated DNA KW - Hydrated electron KW - Hydration shell KW - Hydroxyl radical KW - Indirect damage KW - Ionization KW - LEE KW - Low energy electrons KW - MCS 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 - ROS KW - Radiation damage KW - Radiation therapy KW - Radical KW - Radiolysis KW - Radiotherapy KW - Reactive oxygen species KW - Simulation KW - Single-strand break (SSB) KW - TOPAS KW - TOPAS-nbio KW - XPS KW - Xray KW - Xray photo electron spectrocopy KW - Particle scattering KW - Presolvated electron KW - ESCA PY - 2023 AN - OPUS4-57255 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 - CONF A1 - Hahn, Marc Benjamin T1 - Radiation biophysics: a journey N2 - We give an overview about recent work concerning ionizing radiation damage to Oligonucleotides, plasmid DNA, DNA binding proteins (G5P), and DNA-protein complexes. We focus on combining new experimental setups with Geant4/TOPAS particle scattering simulations to understand the effets of ionizing radiation. T2 - Project update CY - Online meeting DA - 09.10.2023 KW - DNA KW - Proteins KW - G5P KW - Geant4 KW - Geant4-DNA KW - TOPAS KW - TOPAS-nBio KW - LEE KW - Dosimetry KW - Microdosimetry KW - Magnetism KW - Protein PY - 2023 AN - OPUS4-58744 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 - TY - CONF A1 - Hahn, Marc Benjamin A1 - Radnik, Jörg A1 - Dietrich, P. M. T1 - Near-ambient-pressure Xray photoelectron spectroscopy (XPS) to monitor DNA radiation damage directly in water 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 - RADeleven CY - Herceg Novi, Montenegro DA - 19.06.2023 KW - Base damage KW - Base loss KW - Cancer treatment KW - DNA KW - DNA radiation damage KW - Direct damage KW - Dissociative electron attachment (DEA) KW - Dissociative electron transfer (DET) KW - Dosimetry KW - Double-strand break (DSB) KW - ESCA KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Hydrated DNA KW - Hydrated electron KW - Hydrated electrons KW - Hydration shell KW - Hydroxyl radical KW - Indirect damage KW - Ionisation KW - Ionization KW - LEE KW - DEA KW - DET KW - Low energy electrons KW - MCS KW - Microdosimetry KW - NAP-XPS KW - Near ambient pressure xray photo electron spectroscopy KW - Net-ionization reaction KW - OH radical KW - PES KW - Particle scattering KW - Prehydrated electron KW - Presolvated electron KW - Protein KW - Quasi-direct damage KW - ROS KW - Radiation damage KW - Radiation therapy KW - Radical KW - Radiolysis KW - Radiotherapy KW - Reactive oxygen species KW - Simulation KW - Single-strand break (SSB) KW - Single-stranded DNA-binding proteins KW - TOPAS KW - TOPAS-nbio KW - XPS KW - Xray photo electron spectrocopy PY - 2023 AN - OPUS4-57782 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Combined cell and nanoparticle models for TOPAS to study radiation dose enhancement by Monte-Carlo based particle scattering Simulations 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.[1] 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. [2] 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 ongoing experimental work which aims to obtain a mechanistic understanding of cell death induced by radioactive 198Au. T2 - #RSCposter 2023 CY - Online meeting DA - 28.02.2023 KW - AuNP KW - Beta decay KW - Brachytherapy KW - Cancer treatment KW - Clustered nanoparticles KW - DNA KW - DNA damage KW - Dosimetry KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Gold Nanoparticles KW - LEE KW - Livermore model KW - Low energy electrons KW - MCS KW - Microdosimetry KW - Monte-Carlo simulation KW - NP KW - OH radical KW - Penelope model KW - Radiation damage KW - Radiation therapy KW - Radiationtherapy KW - Radiotherapy KW - Radioactive decay KW - Radiolysis KW - Simulation KW - TOPAS KW - TOPAS-nbio KW - beta particle KW - particle scattering PY - 2023 AN - OPUS4-57060 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Meyer, S. A1 - Schröter, M.-A. A1 - Kunte, Hans-Jörg A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - Ectoine protects biomolecules from ionizing radiation: Molecular mechanisms N2 - The compatible solute and osmolyte ectoine is an effective protectant of biomolecules and whole cells against heating, freezing and high salinity. The protection of cells (human Keratinocytes) by ectoine against ultraviolet radiation was also reported by various authors, although the underlying mechanism is not yet understood. We present results on the irradiation of biomolecules (DNA) with ionizing radiation (high energy electrons) in fully aqueous environment in the presence of ectoine and high salt concentrations. The results demonstrate an effective radiation protection of DNA by ectoine against the induction of single strand breaks by ionizing radiation. The effect is explained by an increased in low-energy electron scattering at the enhanced free-vibrational density of states of water due to ectoine, as well as the action of ectoine as an OH-radical scavenger. This was demonstrated by Raman spectroscopy, electron paramagnetic resonance (EPR) and Monte-Carlo simulations (Geant4). T2 - #RSCposter 2023 CY - Online meeting DA - 28.02.2023 KW - Compatible solute KW - Dosimetry KW - Ectoine KW - Ectoin KW - Ectoine radiation protection KW - Ectoine radical scavenger KW - Geant4 KW - Geant4-DNA KW - Hydroxyectoine KW - Hydroxyl radical KW - Ionizing radiation KW - Low energy electrons KW - LEE KW - OH-radical KW - DNA KW - Osmolyte KW - Radiation damage KW - Radiation protection KW - Radical scavenger KW - Radiation therapy PY - 2023 AN - OPUS4-57061 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 - Seitz, H. A1 - Smales, Glen Jacob T1 - Bio-SAXS of single-stranded DNA-binding proteins: Radiation protection by the compatible solute ectoine N2 - Small-angle X-ray scattering (SAXS) can be used for structural determination of biological macromolecules and polymers in their native states (e.g. liquid phase). This means that the structural changes of (bio-)polymers, such as proteins and DNA, can be monitored in situ to understand their sensitivity to changes in chemical environments. In an attempt to improve the reliability of such experiments, the reduction of radiation damage occurring from exposure to X-rays is required. One such method, is to use scavenger molecules to protect macromolecules against radicals produced during radiation exposure, such as reactive oxygen species (ROS). In this study we investigate the feasibility of applying the compatible solute, osmolyte and radiation protector Ectoine (THP(B)), as a scavenger molecule during SAXS measurements of the single-stranded DNA-binding protein Gene-V Protein (G5P/GVP). In this case, we monitor the radiation induced changes of G5P during bio-SAXS measurments and the resulting microscopic energy-damage relation was determined from microdosimetric calculations by Monte-Carlo based particle scattering simulations with TOPAS/Geant4 and a custom target-model. This resulted in a median-lethal energy deposit of pure G5P at 4 mg mL−1 of E1/2 = 7 ± 5 eV, whereas a threefold increase of energy-deposit was needed under the presence of Ectoine to reach the same level of damage. This indicates that Ectoine increases the possible exposure time before radiation-damage to G5P is observed. Furthermore, the dominant type of damage shifted from aggregation in pure solutions towards a fragmentation for solutions containing Ectoine as a cosolute. These results are interpreted in terms of indirect radiation damage by reactive secondary species, as well as post-irradiation effects, related to preferential-exclusion of the cosolute from the protein surface. Hence, Ectoine is shown to provide a non-disturbing way to improve structure-determination of proteins via bio-SAXS in future studies. T2 - #RSCposter 2023 CY - Online meeting DA - 28.02.2023 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 - Particle scattering simulations 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 KW - Topas-MC KW - Topas-nBio KW - X-ray scattering KW - ssDNA KW - Osmolyte KW - Hydroxyectoine KW - Compatible solute KW - ROS KW - radical scavenger PY - 2023 UR - https://pubs.rsc.org/en/content/articlehtml/2023/cp/d2cp05053f AN - OPUS4-57064 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin A1 - Dietrich, Paul M. A1 - Radnik, Jörg T1 - Near-ambient-pressure XPS as as tool to monitor DNA radiation damage directly in water 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 - Miller Conference CY - Furiani, France DA - 03.06.2023 KW - Base damage KW - Base loss KW - Cancer treatment KW - DNA KW - DNA radiation damage KW - Direct damage KW - Dissociative electron attachment (DEA) KW - Dissociative electron transfer (DET) KW - Dosimetry KW - Double-strand break (DSB) KW - ESCA KW - Energy deposit KW - G5P KW - Geant4 KW - Geant4-DNA KW - Hydrated DNA KW - Hydrated electron KW - Hydroxyl radical KW - Indirect damage KW - Ionisation KW - Ionization KW - LEE KW - Low energy electrons KW - MCS KW - Microdosimetry KW - NAP-XPS KW - Near ambient pressure xray photo electron spectroscopy KW - Net-ionization reaction KW - OH radical KW - PES KW - Particle scattering KW - Prehydrated electron KW - Presolvated electron KW - Protein KW - Quasi-direct damage KW - ROS KW - Radiation damage KW - Radiation therapy KW - Radical KW - Radiolysis KW - Radiotherapy KW - Reactive oxygen species KW - Simulation KW - Single-strand break (SSB) KW - Single-stranded DNA-binding proteins KW - TOPAS KW - TOPAS-nbio KW - XPS KW - Xray KW - Xray photo electron spectrocopy KW - Hydration shell PY - 2023 AN - OPUS4-57646 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 - Bio-SAXS of single-stranded DNA-binding proteins: Radiation protection by the compatible solute ectoine N2 - Small-angle X-ray scattering (SAXS) can be used for structural determination of biological macromolecules and polymers in their native states (e.g. liquid phase). This means that the structural changes of (bio-)polymers, such as proteins and DNA, can be monitored in situ to understand their sensitivity to changes in chemical environments. In an attempt to improve the reliability of such experiments, the reduction of radiation damage occurring from exposure to X-rays is required. One such method, is to use scavenger molecules to protect macromolecules against radicals produced during radiation exposure, such as reactive oxygen species (ROS). In this study we investigate the feasibility of applying the compatible solute, osmolyte and radiation protector Ectoine (THP(B)), as a scavenger molecule during SAXS measurements of the single-stranded DNA-binding protein Gene-V Protein (G5P/GVP). In this case, we monitor the radiation induced changes of G5P during bio-SAXS measurments and the resulting microscopic energy-damage relation was determined from microdosimetric calculations by Monte-Carlo based particle scattering simulations with TOPAS/Geant4 and a custom target-model. This resulted in a median-lethal energy deposit of pure G5P at 4 mg mL−1 of E1/2 = 7 ± 5 eV, whereas a threefold increase of energy-deposit was needed under the presence of Ectoine to reach the same level of damage. This indicates that Ectoine increases the possible exposure time before radiation-damage to G5P is observed. Furthermore, the dominant type of damage shifted from aggregation in pure solutions towards a fragmentation for solutions containing Ectoine as a cosolute. These results are interpreted in terms of indirect radiation damage by reactive secondary species, as well as post-irradiation effects, related to preferential-exclusion of the cosolute from the protein surface. Hence, Ectoine is shown to provide a non-disturbing way to improve structure-determination of proteins via bio-SAXS in future studies. KW - BioSAXS KW - Bio-SAXS KW - Cosolute KW - Ectoine KW - G5P KW - GVP KW - Radiation damage KW - Radical Scavenger KW - Single-stranded DNA-binding proteins KW - X-ray scattering KW - DNA KW - ssDNA KW - Protein KW - SAXS KW - Small-angle xray scattering KW - McSAS3 KW - Dosimetry KW - Microdosimetry KW - Geant4 KW - Geant4-DNA KW - Topas KW - Topas-MC KW - Monte-Carlo simulations KW - Particle scattering simulations KW - Topas-nBio KW - OH Radical KW - OH radical scavenger KW - LEE KW - Ionizing radiation damage KW - Protein unfolding KW - Ectoin PY - 2023 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-568909 DO - https://doi.org/10.1039/d2cp05053f SN - 1463-9076 SN - 1463-9084 VL - 25 IS - 7 SP - 5372 EP - 5382 PB - Royal Society of Chemistry CY - Cambridge AN - OPUS4-56890 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -