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Simulation of Cell Survival Probability and Chromosome Aberration Yields Based On a Nanodosimetric Monte Carlo Cell Nucleus Model


B Lee

B Lee12*, C Wang2 , (1) Northwestern Memorial Hospital, Chicago, IL, (2) Georgia Inst of Technology, Atlanta, GA

Presentations

SU-K-FS2-15 (Sunday, July 30, 2017) 4:00 PM - 6:00 PM Room: Four Seasons 2


Purpose: To quantify the yields of cell survival and chromosomal aberration through nanodosimetric analysis of cell nuclei featuring advanced DNA organization exposed to different types of radiation.

Methods: Cell nuclei were simulated in the G0/G1 phase using an improved Monte Carlo code for the stochastic placement of chromatin fibers (CFs) of 30nm diameter within chromatin-dense domains (CDs) of 400nm diameter and a chromatin-sparse interchromatin compartment (IC). These structures are further organized within 46 distinct chromosome territories within the cell nucleus to allow for assessment of likelihoods of DNA misjoining. A particle track library was generated for hydrogen, helium, carbon ions, and photon/electron irradiations with the Geant4-DNA code at varying energies and quantities of dose. Irradiation of the cells was simulated by overlap of particle tracks with the cell nuclei, and clustering algorithms and probability analyses were applied for assessing the simulated production of DSBs. Based on the proximity of DSBs produced in the various DNA structures, the probability of inducing cell death was assessed.

Results: Initial analysis of energy deposition and DSB yields match expected values. Proximity of DSBs based on the originating particle indicates single track effects are pronounced even for sparsely ionizing radiation. Cell survival comparisons demonstrate a higher rate of cell killing for high-LET radiation than low-LET radiation of identical particles, and also differentiate the higher killing potential of protons over helium ions at identical LET as is expected in the literature.

Conclusion: Cell survival curves produced by the Monte Carlo cell nucleus method demonstrate characteristics expected from experimental results. Furthermore, the recent progress indicates the model can be applied to several fields of interest, particularly in updating radiation risk assessments as well as in ion therapy. Current efforts are being made to project the expected yield of chromosomal aberrations of different particle types.


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