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Stochastic multi-scale modelling of biological effects induced by ionizing radiation.
In: (El Naqa, I [Ed.]: A guide to outcome modeling in radiotherapy and oncology). Elsevier, 2017. 147-180 (Radiother. Oncol.)
An overview is given on bottom-up stochastic modeling of radiation-induced effects on sub- cellular and cellular scales with the PARTRAC suite of Monte Carlo codes. PARTRAC simulations start from modeling particle tracks by following individual interactions of the primary as well as all secondary particles with the traversed medium, typically liquid wa- ter as a surrogate for biological material. Dedicated modules then convert these energy deposits to reactive species and follow their diffusion and mutual reactions. Multi-scale models of DNA and chromatin structures in human cell nuclei are implemented, represent- ing DNA double-helix, nucleosomes, chromatin fiber, domains and chromosome territories. By overlapping with the simulated tracks, these target structures are used in assessing ini- tial radiation-induced DNA and chromatin damage both via direct energy depositions and indirectly through attacks of reactive species. DNA fragmentation patterns can be analyzed. In a subsequent module, cellular repair of DNA double-strand breaks by non-homologous end-joining is simulated. Followed is the enzymatic processing as well as spatial mobil- ity of individual broken chromatin ends; correct rejoining, misrejoining, and formation of chromosome aberrations are scored. The chapter is focused on the underlying principles of radiation action in biological systems on subcellular scales and their stochastic mod- eling with PARTRAC. The pieces of experimental information represented in this tool are highlighted, together with numerous independent benchmarking tests against observed data and trends. Future developments are discussed, directed towards extending PARTRAC scope and predictive power, but also towards applications in medical physics and radiation protection.
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Publikationstyp Artikel: Konferenzbeitrag
Schlagwörter Ionizing radiation, particle tracks, radiation quality, cross sections, reactive species, water radiolysis, radiation-induced DNA damage, DNA damage response, non- homologous end-joining, chromosome aberrations, Monte Carlomodeling, bottom-up model, computational biology
ISSN (print) / ISBN 0167-8140
Konferenztitel El Naqa, I [Ed.]: A guide to outcome modeling in radiotherapy and oncology
Zeitschrift Radiotherapy and Oncology
Quellenangaben Seiten: 147-180
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Protection (ISS)