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Modeling Direct and Indirect Action DSBs From Intracellular Gold Nanoparticles Using a Single Cell Model with Complete Human Genome in Geant4

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: investigate the enhancement of double strand breaks (DSBs) from intracellular gold nanoparticles (GNP) using a single cell Geant4 model

Methods: detailed Geant4 single cell model was built using complex DNA geometry and Geant4-DNA extension to record the direct strand breaks (SBs) from energy deposition during the physical stage and indirect SBs from the reactions between hydroxyl radical and 2-deoxyribose during the chemical stage. The size and number of GNPs modeled was a realistic intracellular concentration obtained from published literature and consisted of 12,000 individual GNPs 90 nm in diameter. The intracellular localization of the GNPs was uniformly distributed within 1 µm from the nuclear wall. Geant4-DNA physics with chemistry model extension was used within the cell, and Livermore physics to model the interactions in GNPs. A 100keV and 6MV photon source were using a parallel plane beam taking into account charged particle equilibrium.

Results: 100 keV photon simulation showed a large increase of more than 28% for cell dose when GNPs are in close proximity to the nucleus. The increase in DSB yield was much lower at 13.7%. For 6 MV a much smaller 1.11 % increment in cell dose is observed, however the increment of DSB yield was much higher at 5.86%. For 6MV the increase of indirect strand breaks plays a more important role, increasing by 8.5%, about two times the direct stand breaks (4.1%).

Conclusion: results show the importance of investigating indirect action SBs using a realistic cell model. It is difficult to study the radiosensitization mechanism from physical dose enhancement alone, especially for clinically relevant high energy sources. In order to further understand the role of GNPs and the possible mechanisms involved in the GNPs induced radiosensitization effect, more sophisticated models that consider chemical interactions should be implemented.

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Keywords

Monte Carlo, Simulation, Radiobiology

Taxonomy

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

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