Relative Role of Physical Mechanisms on Complex Biodamage Induced by Carbon Irradiation

Abstract

The effective use of swift ion beams in cancer treatment (known as hadrontherapy) as well as appropriate protection in manned space missions rely on the accurate understanding of the energy delivery to cells that damages their genetic information. The key ingredient characterizing the response of a medium to the perturbation induced by charged particles is its electronic excitation spectrum. By using linear-response time-dependent density functional theory, we obtained the energy and momentum transfer excitation spectrum (the energy-loss function, ELF) of liquid water (the main constituent of biological tissues), which was in excellent agreement with experimental data. The inelastic scattering cross sections obtained from this ELF, together with the elastic scattering cross sections derived by considering the condensed phase nature of the medium, were used to perform accurate Monte Carlo simulations of the energy deposited by swift carbon ions in liquid water and carried away by the generated secondary electrons, producing inelastic events such as ionization, excitation, and dissociative electron attachment (DEA). The latter are strongly correlated with cellular death, which is scored in sensitive volumes with the size of two DNA convolutions. The sizes of the clusters of damaging events for a wide range of carbon-ion energies, from those relevant to hadrontherapy up to those for cosmic radiation, predict with unprecedented statistical accuracy the nature and relative magnitude of the main inelastic processes contributing to radiation biodamage, confirming that ionization accounts for the vast majority of complex damage. DEA, typically regarded as a very relevant biodamage mechanism, surprisingly plays a minor role in carbon-ion induced clusters of harmful events.

Binary-Encounter Model for Direct Ionization of Molecules by Positron-Impact

“…The BEB-model from this paper can help to disentangle the data further. Such cross section data are important for simulations of the effects of ion-beams on biological materials that are currently limited to secondary electrons (see, e.g., Taioli et al [25]).…”

Inelastic scattering of electrons in water from first principles: cross sections and inelastic mean free path for use in Monte Carlo track-structure simulations of biological damage

“…A previous real-time TDDFT study by Tavernelli [61] presented a dielectric constant of liquid water (optical limit only) with two prominent peaks as opposed to only one main peak in the experimental data [37]. A more recent work by Taioli et al [62] presented linear-response TDDFT (LR-TDDFT) calculations of the ELF for a small water sample of 32 molecules generated via classical molecular dynamics simulations, with XC effects considered in the adiabatic generalized gradient approximation (AGGA), and have shown a good agreement with experiments. But a complete set of ab-initio data as needed by Monte Carlo simulations, including the inelastic mean free path and the electronic stopping power, is still lacking.…”

“…Using an efficient iterative method based on LR-TDDFT and a linear combination of atomic orbitals (LCAO) incorporated in the mbpt-lcao code [63,64] we calculated the ELF of liquid water in a range of finite values of the momentum transfer. The electron-electron interactions were considered at the RPA level in the linear response, unlike in the work by Taioli et al [62], who used the AGGA. RPA yields the correct asymptotic behavior for the long-range interactions, and for an extended system, as the one considered in this work, the difference between RPA and AGGA should not be significant [65].…”

Electronic excitation spectra of cerium oxides: from ab initio dielectric response functions to Monte Carlo electron transport simulations

“…In principle, to determine the inelastic scattering cross-section one needs to know the dependence of the ELF over the entire spectrum of meaningful excitation energies W and momentum transfer q. 43,46,53,66 However, typically one has access only to a limited range of energies, corresponding to those of the valence electrons (t100 eV), owing to the prohibitive computational effort of including high-energy excitations as well as their momentum dispersion. Thus, to extend the excitation energy range beyond the valence regime, we propose to use the MELF-GOS model, [51][52][53][54] which implements a numerically effective and accurate method to compute the ELF over the entire Bethe surface (i.e., the momentum and energy transfer plane) by including both valence and inner shell electronic excitations.…”

“…Typically, elastic scattering occurs between electrons and the massive ionic constituents of the target, and results only in the deflection of electron trajectories. While in principle relativistic first-principles quantum mechanical calculations based on the formal theory of scattering 47,49 can be used to calculate the DESCS, 66 the computational cost to include a large number of atoms required to carry out accurate relativistic simulations in a solid is prohibitive. Thus, we use the expression of the Mott's cross-section (see eqn (14) and ( 15)) within the cluster method, by which we carve out a portion of the material (which can be as small as one atom) and reckon the DESCS only dealing with a molecular cluster surrounded by empty space.…”