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Quantifying 8-oxodG and thymine glycol clusters in reduced-scale human chromatin models using Geant4-DNA.
Tu Minh Khuong1,2, Jong-Hyun Jung1, Sangyong Lim1,2
1Radiation Biotechnology Division, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea.
Physics in Medicine and Biology
|December 4, 2025
Summary
This study enhances Geant4-DNA simulations for radiation-induced oxidative base damage (BD), accurately quantifying specific lesions like 8-oxodG and thymine glycol (Tg) in human cells. The improved model offers a biologically realistic framework for assessing mutagenic risk from low-LET radiation.
Area of Science:
- Radiation biology
- Monte Carlo simulations
- DNA damage modeling
Background:
- Radiation exposure can cause oxidative base damage (BD) to DNA, contributing to mutagenic risk.
- Accurate modeling of specific DNA lesions, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and thymine glycol (Tg), is crucial for understanding biological consequences.
- Existing Monte Carlo frameworks require enhancement for lesion-specific yield quantification.
Purpose of the Study:
- To improve the Geant4-DNA framework for simulating radiation-induced oxidative base damage (BD).
- To quantify lesion-specific yields of 8-oxodG and Tg from indirect radiation effects.
- To develop biologically realistic chromatin models for practical simulations.
Main Methods:
- Integrated custom code into Geant4-DNA to track hydroxyl radical (OH∙)-induced oxidation events by base type.
- Developed reduced-scale chromatin geometries (minihumanA, minihumanB) to maintain DNA density while reducing cell size.
- Simulated Co-60 gamma-rays and protons, sampling millions of primary histories to determine lesion yields from dose-response curves.
Main Results:
- Simulated 8-oxodG yields for Co-60 gamma irradiation were consistent with experimental values reported for human cell lines.
- Predicted thymine glycol (Tg) to double-strand break (DSB) ratios aligned with Nth-sensitive lesion data.
- The minihuman models demonstrated biological relevance and feasibility for Geant4-DNA simulations.
Conclusions:
- The enhanced Geant4-DNA framework with lesion-specific tracking and reduced chromatin geometries provides a feasible and biologically realistic approach to simulating oxidative BD.
- This methodology enables practical simulations for studying non-double-strand break (non-DSB) clustering relevant to mutagenic risk.
- The study validates the model's ability to accurately predict DNA lesion yields under low-linear energy transfer irradiation conditions.
