Purpose: This study aims to develop a comprehensive simulation framework to connect radiation effects from the microscopic to the nanoscopic scale. Method: The process begins with a Geant4-DNA simulation based on the example ”molecularDNA”, producing a dataset of twelve different types of early DNA damages within an Escherichia coli (E. coli) bacterium, generated by proton irradiation at different kinetic energies, giving a nano-scale view of the particle–matter interaction. Then we pass to the micro-scale with a Geant4 simulation, based on the example ”radiobiology”, providing a microscopic view of proton interactions with matter through the Linear Energy Transfer (LET). Then GANDALF (Generative ANsatz for DNA damage evALuation and Forecast) Machine Learning (ML) toolkit, a Neural Network (NN)-based regression system, is employed to correlate the micro-scale LET data with the nano-scale occurrences of DNA damages in the E. coli bacterium. Results: The trained ML algorithm provides a practical tool to convert LET curves versus depth in a water phantom into DNA damage curves for twelve distinct types of DNA damage. To assess the performance, we evaluated the choice and optimization of the regression system based on its interpolation and extrapolation capabilities, ensuring the model could reliably predict DNA damage under various conditions. Conclusions: Through the synergistic integration of Geant4, Geant4-DNA and ML, the study provides a tool to easily convert the results at the micro-scale of Geant4 to those at the nano-scale of Geant4-DNA without having to deal with the high CPU time requirements of the latter.

Purpose: Based on considerable interest to enlarge the experimental database of radioresistant cells after their irradiation with helium ions, HTB140, MCF-7 and HTB177 human malignant cells are exposed to helium ion beams having different linear energy transfer (LET). Materials and methods: The cells are irradiated along the widened 62 MeV/u helium ion Bragg peak, providing LET of 4.9, 9.8, 23.4 and 36.8 keV/µm. Numerical simulations with the Geant4 toolkit are used for the experimental design. Cell survival is evaluated and compared with reference γ-rays. DNA double strand breaks are assessed via γ-H2AX foci. Results: With the increase of LET, surviving fractions at 2 Gy decrease, while RBE (2 Gy, γ) gradually increase. For HTB140 cells, above the dose of 4 Gy, a slight saturation of survival is observed while the increase of RBE (2 Gy, γ) remains unaffected. With the increase of LET the increase of γ-H2AX foci is revealed at 0.5 h after irradiation. There is no significant difference in the number of foci between the cell lines for the same LET. From 0.5 to 24 h, the number of foci drops reaching its residual level. For each time point, there are small differences in DNA DSB among the three cell lines. Conclusion: Analyses of data acquired for the three cell lines irradiated by helium ions, having different LET, reveal high elimination capacity and creation of a large number of DNA DSB with respect to γ-rays, and are between those reported for protons and carbon ions.