Track structures and resulting DNA damage in human cells have been simulated for hydrogen, helium, carbon, nitrogen, oxygen and neon ions with 0.25–256 MeV/u energy. The needed ion interaction cross sections have been scaled from those of hydrogen; Barkas scaling formula has been refined, extending its applicability down to about 10 keV/u, and validated against established stopping power data. Linear energy transfer (LET) has been scored from energy deposits in a cell nucleus; for very low-energy ions, it has been defined locally within thin slabs. The simulations show that protons and helium ions induce more DNA damage than heavier ions do at the same LET. With increasing LET, less DNA strand breaks are formed per unit dose, but due to their clustering the yields of double-strand breaks (DSB) increase, up to saturation around 300 keV/μm. Also individual DSB tend to cluster; DSB clusters peak around 500 keV/μm, while DSB multiplicities per cluster steadily increase with LET. Remarkably similar to patterns known from cell survival studies, LET-dependencies with pronounced maxima around 100–200 keV/μm occur on nanometre scale for sites that contain one or more DSB, and on micrometre scale for megabasepair-sized DNA fragments.

The understanding of the impact of radiation quality in early and late responses of biological targets to ionizing radiation exposure necessarily grounds on the results of mechanistic studies starting from physical interactions. This is particularly true when, already at the physical stage, the radiation field is mixed, as it is the case for neutron exposure. Neutron Relative Biological Effectiveness (RBE) is energy dependent, maximal for energies ~1 MeV, varying significantly among different experiments. The aim of this work is to shed light on neutron biological effectiveness as a function of field characteristics, with a comprehensive modeling approach: this brings together transport calculations of neutrons through matter (with the code PHITS) and the predictive power of the biophysical track structure code PARTRAC in terms of DNA damage evaluation. Two different energy dependent neutron RBE models are proposed: the first is phenomenological and based only on the characterization of linear energy transfer on a microscopic scale; the second is purely ab-initio and based on the induction of complex DNA damage. Results for the two models are compared and found in good qualitative agreement with current standards for radiation protection factors, which are agreed upon on the basis of RBE data.

The calculation algorithm of a modern treatment planning system for ion-beam radiotherapy should ideally be able to deal with different ion species (e.g. protons and carbon ions), to provide relative biological effectiveness (RBE) evaluations and to describe different beam lines. In this work we propose a new approach for ion irradiation outcomes computations, the beamlet superposition (BS) model, which satisfies these requirements. This model applies and extends the concepts of previous fluence-weighted pencil-beam algorithms to quantities of radiobiological interest other than dose, i.e. RBE- and LET-related quantities. It describes an ion beam through a beam-line specific, weighted superposition of universal beamlets. The universal physical and radiobiological irradiation effect of the beamlets on a representative set of water-like tissues is evaluated once, coupling the per-track information derived from FLUKA Monte Carlo simulations with the radiobiological effectiveness provided by the microdosimetric kinetic model and the local effect model. Thanks to an extension of the superposition concept, the beamlet irradiation action superposition is applicable for the evaluation of dose, RBE and LET distributions. The weight function for the beamlets superposition is derived from the beam phase space density at the patient entrance. A general beam model commissioning procedure is proposed, which has successfully been tested on the CNAO beam line. The BS model provides the evaluation of different irradiation quantities for different ions, the adaptability permitted by weight functions and the evaluation speed of analitical approaches. Benchmarking plans in simple geometries and clinical plans are shown to demonstrate the model capabilities.

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Comprehensive track structure-based simulations of DNA damage induced in human cells by photons (5 keV -1.3 MeV) and light ions (0.25 -512 MeV/u) were performed with PARTRAC. DNA strand breaks, double-strand breaks, and their clustering were scored. Effective LET values were established for photons that provide LET-dependent damage yields in agreement with the data for ions. The resulting database captures the variations of biological effectiveness with radiation quality. In particular, it can help compare the effectiveness of conventional radiotherapy using photon beams with techniques relying on proton or ion beams.

Mitochondrial DNA does not represent a critical target for radiation effects. Likely, the key role of mitochondria in radiation-induced biological effects arises from the communication between mitochondria and/or with the nucleus. Through this signaling, initial modifications in a few heavily hit mitochondria seem to be amplified to a massive long-term effect manifested in the whole cell or even tissue.

Radiation damage by low-energy ions significantly contributes to the high biological efficiency of ion beams in distal Bragg peak regions as well as to the energy-dependent efficiency of neutron irradiation. To enable assessing biological effects of ions at energies <1 MeV u(-1) with track-structure based models, a Barkas-like scaling procedure is developed that provides ion cross sections in liquid water based on those for hydrogen ions. The resulting stopping power and range for carbon ions agree with the ICRU 73 database and other low-energy stopping power data. The method represents the basis for extending PARTRAC simulations of light ion track structures and biological effects down to the keV u(-1) range.

The biophysical simulation tool PARTRAC contains modules for DNA damage response representing non-homologous end joining of DNA double-strand breaks (DSB) and the formation of chromosomal aberrations. Individual DNA ends from the induced DSB are followed regarding both their enzymatic processing and spatial mobility, as is needed for chromosome aberrations to arise via ligating broken ends from different chromosomes. In particular, by tracking the genomic locations of the ligated fragments and the positions of centromeres, the induction of dicentrics can be modelled. In recent experiments, the impact of spatial clustering of DNA damage on dicentric yields has been assessed in AL human-hamster hybrid cells: Defined numbers of 20 MeV protons (linear energy transfer, LET 2.6 keV/µm), 45 MeV Li ions (60 keV/µm) and 55 MeV C ions (310 keV/µm) focused to sub-µm spot sizes were applied with the ion microbeam SNAKE in diverse grid modes, keeping the absorbed dose constant. The impact of the µm-scaled spatial distribution of DSB (focusing effect) has thus been separated from nm-scaled DSB complexity (LET effect). The data provide a unique benchmark for the model calculations. Model and parameter refinements are described that enabled the simulations to largely reproduce both the LET-dependence and the focusing effect as well as the usual biphasic rejoining kinetics. The predictive power of the refined model has been benchmarked against dicentric yields for photon irradiation.