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Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue.

Mirsch, Johanna and Tommasino, Francesco and Frohns, Antonia and Conrad, Sandro and Durante, Marco and Scholz, Michael and Friedrich, Thomas and Löbrich, Markus :
Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue.
In: Proceedings of the National Academy of Sciences of the United States of America, 112 (40) pp. 12396-12401. ISSN 1091-6490
[Article] , (2015)

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/r(2) 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.

Item Type: Article
Erschienen: 2015
Creators: Mirsch, Johanna and Tommasino, Francesco and Frohns, Antonia and Conrad, Sandro and Durante, Marco and Scholz, Michael and Friedrich, Thomas and Löbrich, Markus
Title: Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue.
Language: English
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/r(2) 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.

Journal or Publication Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 112
Number: 40
Divisions: 10 Department of Biology
10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 01 Oct 2015 06:43
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