title: Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue.
abstract: Charged particles are increasingly used in cancer radiotherapy and contribute significantly to the natural radiation risk. The difference in the biological effects of high-energy charged particles compared with X-rays or γ-rays is determined largely by the spatial distribution of their energy deposition events. Part of the energy is deposited in a densely ionizing manner in the inner part of the track, with the remainder spread out more sparsely over the outer track region. Our knowledge about the dose distribution is derived solely from modeling approaches and physical measurements in inorganic material. Here we exploited the exceptional sensitivity of γH2AX foci technology and quantified the spatial distribution of DNA lesions induced by charged particles in a mouse model tissue. We observed that charged particles damage tissue nonhomogenously, with single cells receiving high doses and many other cells exposed to isolated damage resulting from high-energy secondary electrons. Using calibration experiments, we transformed the 3D lesion distribution into a dose distribution and compared it with predictions from modeling approaches. We obtained a radial dose distribution with sub-micrometer resolution that decreased with increasing distance to the particle path following a 1/r2 dependency. The analysis further revealed the existence of a background dose at larger distances from the particle path arising from overlapping dose deposition events from independent particles. Our study provides, to our knowledge, the first quantification of the spatial dose distribution of charged particles in biologically relevant material, and will serve as a benchmark for biophysical models that predict the biological effects of these particles.
authors.affiliation: Radiation Biology and DNA Repair, Darmstadt University of Technology, 64287 Darmstadt, Germany;
authors.forename: Johanna
authors.initials: J
authors.lastname: Mirsch
authors.affiliation: Department of Biophysics, GSI Helmholtz Center for Heavy Ion Research, 64291 Darmstadt, Germany;
authors.forename: Francesco
authors.initials: F
authors.lastname: Tommasino
authors.affiliation: Radiation Biology and DNA Repair, Darmstadt University of Technology, 64287 Darmstadt, Germany;
authors.forename: Antonia
authors.initials: A
authors.lastname: Frohns
authors.affiliation: Radiation Biology and DNA Repair, Darmstadt University of Technology, 64287 Darmstadt, Germany;
authors.forename: Sandro
authors.initials: S
authors.lastname: Conrad
authors.affiliation: Department of Biophysics, GSI Helmholtz Center for Heavy Ion Research, 64291 Darmstadt, Germany; Institute for Condensed Matter Physics, Darmstadt University of Technology, 64289 Darmstadt, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Durante
authors.affiliation: Department of Biophysics, GSI Helmholtz Center for Heavy Ion Research, 64291 Darmstadt, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Scholz
authors.affiliation: Department of Biophysics, GSI Helmholtz Center for Heavy Ion Research, 64291 Darmstadt, Germany; t.friedrich@gsi.de lobrich@bio.tu-darmstadt.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Friedrich
authors.affiliation: Radiation Biology and DNA Repair, Darmstadt University of Technology, 64287 Darmstadt, Germany; t.friedrich@gsi.de lobrich@bio.tu-darmstadt.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Löbrich
mesh_terms: D000512:Alpha Particles; D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D006657:Histones / Q000378:metabolism; D008810:Mice, Inbred C57BL; D012160:Retina / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D046509:Tissue Culture Techniques; D014965:X-Rays
chemical_list: D006657:Histones; C475961:gamma-H2AX protein, mouse; D004247:DNA
keywords: biodosimetry; charged particles; local effect model; radial dose distribution; γH2AX foci