A combined Monte Carlo and experimental approach to correct foci overlap in quantifying carbon-ion-induced DNA...

Based on Monte Carlo simulations and biological experiments, this study aimed to quantitatively analyze the spatial distribution and complexity of DNA double-strand breaks (DSBs) induced by carbon-ion radiation.

Using X-rays as the reference radiation, γ-H2AX immunofluorescence assays combined with Monte Carlo simulations were performed to evaluate the spatial distribution and complexity of DNA damage in HeLa cells exposed to radiation with different linear energy transfer (LET) values. To analyze the number and size distribution of fluorescent foci, the biological experiments used radiation doses of 0.5 Gy, 1 Gy, and 2 Gy, respectively. Monte Carlo simulations were conducted using Geant4-DNA and TOPAS. DNA damage clusters were quantitatively analyzed using an improved dose-weighted DBSCAN algorithm.

Experimental results showed that X-rays primarily induced small, spatially dispersed DNA lesions, whereas high-LET carbon ions caused dense, overlapping complex damage. The simulated and experimental results matched well for X-rays, but carbon ion irradiation showed a nonlinear correlation between damage clusters and foci size. Further analysis indicated that carbon ion-induced damage involving both "intra-track" and "inter-track" mechanisms. At equal doses, higher particle fluence in shallow regions led to more inter-track damage, compensating for lower single-particle radiation quality. A dose-dependent Ratio Factor was proposed and validated to correct the simulated and experimental data, as described by the regression equation: Ratio Factor = (0.74 ± 0.03) × Dose + (0.67 ± 0.01).

This study clarified the spatial distribution characteristics of carbon-ion-induced DNA damage under various radiation conditions, and proposed a novel correction model for accurate prediction of DNA damage clusters, potentially applicable to carbon-ion radiotherapy.