{"paper_id":"06064d03-bce4-4e79-8cbb-7175dcde82b2","body_text":"Ultra-High Dose-Rate Irradiation Spares DNA under Physiological Oxygen and Salt Conditions | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Ultra-High Dose-Rate Irradiation Spares DNA under Physiological Oxygen and Salt Conditions Marc Benjamin Hahn, Sepideh Aminzadeh-Gohari, Anna Grebinyk, Matthias Gross, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9566633/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Cancer treatment with radiotherapy aims to kill tumor cells while sparing healthy tissue. Therefore,the experimentally observed sparing of healthy tissue by the FLASH effect during ultra-high dose rate (UHDR) irradiations enables clinicians to extend the therapeutic window. However, the underlying chemical mechanisms are far from being understood. DNA is the main molecular targets for radiotherapy. Here radiation-damage to DNA depends strongly on solvent conditions. We irradiated plasmid DNA pUC19, with 18MeV electrons at conventional/low-dose-rates(LDR) and UHDR under tightly controlled ambient and physiological oxygen conditions in phosphate-buffered-saline (PBS). For the first time, a sparing effect of DNA strand-break induction between UHDR and LDR irradiated DNA under physiological oxygen, salt and pH7.4 is observed. Under physiological oxygen (physoxia≈5%O2,40mmHg), more single-strand-breaks(SSB) and double-strand-breaks(DSB) are observed when exposed with LDR than UHDR. This behaviour is absent for ambient oxygen (normoxia,≈21%O2,150-160mmHg). Additional Geant4/TOPAS-nBio based particle-scattering and radiation-chemical Monte-Carlo simulations helped to determine radical-yields and reactive-oxygen-species(ROS). A model for the observed DNA sparing under FLASH conditions at physoxia was proposed: The interplay of O2 with the •OH-induced hydrogen-abstraction at the sugar-phosphate-backbone, and the conversion of DNA-base-damage to SSB, under consideration of the dose-rate-dependent H3O+ yield via beta-elimination processes is accounted for,to explain the observed behavior. Physical sciences/Chemistry/Physical chemistry/Biophysical chemistry Physical sciences/Chemistry/Physical chemistry/Reaction kinetics and dynamics Full Text Additional Declarations There is NO Competing Interest. Supplementary Files supplementaryinformation.pdf Supplementary Figures and Methods Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-9566633\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":636710554,\"identity\":\"60a9d27b-ee91-4209-8d30-f0fd884b09df\",\"order_by\":0,\"name\":\"Marc Benjamin 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