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Session: Advanced Dosimetry and Monte Carlo Simulation [Return to Session]

Developing and Implementing Metaphase DNA Model for Microscopic Monte Carlo Simulation Based Radiation-Induced DNA Damage Calculation

S Sitmukhambetov, B Dinh, Y Chi*, University of Texas at Arlington, Arlington, TX

Presentations

WE-C930-IePD-F3-5 (Wednesday, 7/13/2022) 9:30 AM - 10:00 AM [Eastern Time (GMT-4)]

Exhibit Hall | Forum 3

Purpose: DNA geometry modeling in radiobiology simulation plays an important role. As currently only the G0/G1 phase DNA model is avail able in microscopic Monte Carlo (MC) simulation, this study proposes to implement a metaphase model for radiation-induced DNA damage study in microscopic MC simulation.

Methods: We generated a two-turn metaphase DNA model using loop extrusion in a dimension of 418 nm in height and 352 nm in radius, containing 120,000 monomers. Each monomer represents one nucleosome containing 200 base-pairs. The geometry was voxelized into 11x11x11 nm3 cubes and distributed for GPU to compute the DNA damage events. Each voxel contains a nucleosome of one of the two types and overall 30 different orientations. There is a straight type, connecting centers of opposite sides of the voxel and a bent type that connects centers of adjacent sides of the voxel. These two types can be rotated to represent connections between any two adjacent nucleosomes. Then, each nucleosome can be readily connected into a chain that represents a DNA chromosome. GPU-based MC computational platform gMicroMC is used to calculate different types of DNA damages of the cell. We considered DNA damages from a) 30 9kV electrons and b) 10 6kV electrons. In both cases, DNA damage events for metaphase and G0/G1 phase were computed and compared.

Results: We simulated the nucleosome geometry and geometry of the DNA in the metaphase. For case a), we obtained 55 single-strand-breaks (SSBs) and 4 double-strand-breaks (DSBs) for metaphase and 47 SSBs and 1 DSBs for G0/G1 phase, while it was 17 v.s. 11 SSBs for case 2. We interpreted the results as the denser distribution of the metaphase inevitably received more local damages than the spread-out DNA configuration for the G0/G1 phase.

Conclusion: We successfully developed and implemented a metaphase DNA model for gMicroMC simulation.

Funding Support, Disclosures, and Conflict of Interest: 1R15CA256668-01A1

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