Quantifying 8-oxodG and thymine glycol clusters in reduced-scale human chromatin models using Geant4-DNA

<i>Objective.</i>This work enhances the Geant4-DNA Monte Carlo framework for modeling radiation-induced oxidative base damage (BD) by quantifying lesion-specific yields of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and thymine glycol (Tg), accounting only for the contribution of indirect effects.<i>Approach.</i>A custom code was integrated into the Geant4-DNA chemical stage to categorize hydroxyl radical (OH∙)-induced oxidation events by base type. When anOH∙radical interacts with DNA, the algorithm identifies whether the target is guanine or thymine and applies site-specific probabilities for forming 8-oxodG or Tg, respectively, without modifying the underlying independent reaction time method. Two reduced-scale chromatin geometries (minihumanA and minihumanB) were constructed to preserve DNA density while reducing overall cell dimensions, enabling simulations across different radiation types, including Co-60<i>γ</i>-rays and protons. Radiation interactions were sampled over3×108-10⁹primary histories, and lesion yields were obtained from the slope of dose-response curves plotting lesions per base pair against absorbed dose. Post-processing classified non-double-strand-break (non-DSB) clusters based on the positions of DSBs, single-strand breaks, and BDs.<i>Main results.</i>For Co-60<i>γ</i>irradiation, simulated 8-oxodG yields were0.0165±0.0004and0.0144±0.0011per 10⁶bases per Gy for minihumanA and minihumanB, respectively-consistent with experimental values of 0.0095-0.020 per 10⁶bases per Gy reported for THP-1 and human fibroblast cells by other groups. The predicted Tg/DSB ratios,1.064±0.026and0.917±0.083, aligned with Nth-sensitive lesion data, reinforcing the model's biological relevance.<i>Significance.</i>The combination of lesion-specific chemical tracking and reduced-size chromatin geometries provides a feasible, biologically realistic framework for simulating oxidative BD in human cells. By maintaining DNA density while decreasing cell dimensions, the minihuman models preserve the characteristics of the reference geometry and enable practical use of Geant4-DNA to study non-DSB clustering relevant to mutagenic risk under low-linear energy transfer irradiation.