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Single Cell Model with Complete Human Genome Using Geant4-DNA to Quantify Direct and Indirect Action Double-Strand Breaks

X Zhao*, R Liu, T Zhao, F Reynoso, Washington University in St. Louis, St. Louis, MO

Presentations

(Sunday, 7/12/2020)   [Eastern Time (GMT-4)]

Room: AAPM ePoster Library

Purpose: quantify DNA double strand breaks (DSBs) using a single cell Geant4 model with complete human genome, and a mechanistic model of radiation chemistry in Geant4-DNA extension.

Methods: single cell model was implemented representing the cell in the G0/G1 phase of the cycle, and its nucleus filled with compacted DNA structure to represent the complete human genome using a total of 6 Gbp. Early reactions between DNA molecules and radical were added in a separate chemical stage modeled at 2.5 ns. Thereby, the cell model was able to record the energy deposition during the physical stage as direct strand breaks (SBs), and indirect SBs during the chemical stage. In this work, only reactions between hydroxyl radicals and 2-deoxyribose are considered. A Co-60 photon source and proton beams between 1-100 MeV were used. A clustering algorithm was implemented in order to quantify DSBs, which are the most critical damage generated by ionizing radiation to DNA.

Results: Co60 the DSB yield is 9.168±0.416 DSB/Gy/Gbp and the proportion of indirect SBs is 77.9% of the total SBs, about 3.5 times the direct SBs. For protons with different energies, the DSB yield monotonically decrease with energy from 14.15±0.13 DSB/Gy/Gbp for 1 MeV and down to 8.19±0.64 DSB/Gy/Gbp for 100 MeV. General agreement with published literature was observed over the whole simulated proton energy range and the Co60 beam on the yield of DSB/Gy/Gbp.

Conclusion: results presented indicated that the single cell model accurately simulates the radiation-induced DNA damage, and shows that indirect SBs play an important role in the construction of DNA damage. The simulation of indirect SBs’ contribution in DNA damage can improve the understanding of the mechanisms involved in the generation of DNA damage. This type of framework is needed to investigate radiosensitization from metallic nanostructures.

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Keywords

Monte Carlo, Radiobiology, Simulation

Taxonomy

TH- Radiobiology(RBio)/Biology(Bio): RBio- general

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