Modeling ionizing radiation interaction with biological matter is a major scientific challenge, especially for protons that are nowadays widely used in cancer treatment. That presupposes a sound understanding of the mechanisms that take place from the early events of the induction of DNA damage. Herein, we present results of irradiation-induced complex DNA damage measurements using plasmid pBR322 along a typical Proton Treatment Plan at the MedAustron proton and carbon beam therapy facility (energy 137-198 MeV and Linear Energy Transfer (LET) range 1-9 keV/μm), by means of Agarose Gel Electrophoresis and DNA fragmentation using Atomic Force Microscopy (AFM). The induction rate Mbp-1 Gy-1 for each type of damage, single strand breaks (SSBs), double-strand breaks (DSBs), base lesions and non-DSB clusters was measured after irradiations in solutions with varying scavenging capacity containing 2-amino-2-(hydroxymethyl)propane-1,3-diol (Tris) and coumarin-3-carboxylic acid (C3CA) as scavengers. Our combined results reveal the determining role of LET and Reactive Oxygen Species (ROS) in DNA fragmentation. Furthermore, AFM used to measure apparent DNA lengths provided us with insights into the role of increasing LET in the induction of highly complex DNA damage.

2nd Department of Radiology Medical School National and Kapodistrian University of Athens 11517 Athens Greece

Atominstitut Technische Universität Wien 1020 Vienna Austria

DNA Damage Laboratory Physics Department School of Applied Mathematical and Physical Sciences National Technical University of Athens 15780 Athens Greece

Nuclear Physics Institute Czech Academy of Sciences Na Truhlářce 39 64 180 86 Prague Czech Republic

Radiation Institute for Science and Engineering Prairie View A and M University Prairie View TX 77446 USA

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