Integrating experimental data and modeling to unravel cell damage responses in monoenergetic neutron fields

Human exposure to mixed ionizing radiation fields presents challenges in understanding subcellular effects due to heterogeneous energy deposition. This study investigates DNA damage in primary endothelial cells exposed to monoenergetic neutrons (2.5 or 15.1 MeV), which generate complex secondary charged particle fields.

Cells were irradiated on a human torso water phantom at 0.13 or 2.11 cm mean depth, 3.20 cm from the neutron source. Three independent experiments were performed per setup at low absorbed doses (<0.12 Gy), estimated from neutron fluence and Monte Carlo simulations (Geant4). DNA damage was assessed by $\gamma$-H2AX foci formation 30 minutes post-irradiation.

Both experimental and simulation data showed higher foci yields at 2.5 MeV compared with 15.1 MeV across all geometries. Simulated DNA DSBs and foci per nucleus increased with dose within the investigated low-dose range (≤0.14 Gy). DSB induction was 37.5-38.6 DSBs per nucleus per Gy at 2.5 MeV versus 22.2-26.5 at 15.1 MeV. Simulated foci yields ranged from 14.3 to 21.7 foci per nucleus per Gy, agreed with experimental results despite dose variability. These findings are in line with the ICRP's energy-dependent weighting factors, indicating greater biological impact at lower neutron energies. Linear foci patterns, observed in 3.9-18.6% of nuclei, appeared perpendicular to neutron incidence. MINAS TIRITH simulations linked these tracks to secondary protons (LET_modal ∼4-19 keV·µm^-1) and $\alpha$ particles at 15.1 MeV neutrons (LET_modal ∼58-107 keV·µm^-1).

This study advances understanding of energy-dependent biological effects in neutron fields, and highlighting the complex, heterogeneous nature of low-dose neutron exposure.