G. Baiocco

Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping

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.

Galactic cosmic ray simulation at the NASA Space Radiation Laboratory

Most accelerator-based space radiation experiments have been performed with single ion beams at fixed energies. However, the space radiation environment consists of a wide variety of ion species with a continuous range of energies. Due to recent developments in beam switching technology implemented at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), it is now possible to rapidly switch ion species and energies, allowing for the possibility to more realistically simulate the actual radiation environment found in space. The present paper discusses a variety of issues related to implementation of galactic cosmic ray (GCR) simulation at NSRL, especially for experiments in radiobiology. Advantages and disadvantages of different approaches to developing a GCR simulator are presented. In addition, issues common to both GCR simulation and single beam experiments are compared to issues unique to GCR simulation studies. A set of conclusions is presented as well as a discussion of the technical implementation of GCR simulation.

GARFIELD + RCo digital upgrade: A modern set-up for mass and charge identification of heavy-ion reaction products

An upgraded GARFIELD + Ring Counter (RCo) apparatus is presented with improved performances as far as electronics and detectors are concerned. On the one hand fast sampling digital read out has been extended to all detectors, allowing for an important simplification of the signal processing chain together with an enriched extracted information. On the other hand a relevant improvement has been made in the forward part of the set-up (RCo): an increased granularity of the CsI(Tl) crystals and a higher homogeneity in the silicon detector resistivity. The renewed performances of the GARFIELD + RCo array make it suitable for nuclear reaction measurements both with stable and with Radioactive Ion Beams (RIB), like the ones planned for the SPES facility, where the physics of isospin can be studied.

Non-statistical decay and α-correlations in the 12C+ 12C fusion-evaporation reaction at 95 MeV

Multiple alpha coincidences and correlations are studied in the reaction 12C+12C at 95 MeV for fusion–evaporation events completely detected in charge. Two specific channels with carbon and oxygen residues in coincidence with α −particles are addressed, which are associated with anomalously high branching ratios with respect to the predictions of Hauser–Feshbach calculations. Triple alpha emission appears kinematically compatible with a sequential emission from a highly excited Mg. The phase space distribution of α − α coincidences suggests a correlated emission from a Mg compound, leaving an oxygen residue excited above the threshold for neutron decay. These observations indicate a preferential α emission of 24Mg at excitation energies well above the threshold for 6 − α decay.

The origin of neutron biological effectiveness as a function of energy

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.

Thermal properties of light nuclei from 12C + 12C fusion–evaporation reactions

The 12C + 12C reaction at 95 MeV has been studied through the complete charge identification of its products by means of the GARFIELD+RCo experimental set-up at INFN Laboratori Nazionali di Legnaro (LNL). In this paper, the first of a series of two, a comparison to a dedicated Hauser–Feshbach calculation allows selecting a set of dissipative events which corresponds, to a large extent, to the statistical evaporation of highly excited 24Mg. Information on the isotopic distribution of the evaporation residues in coincidence with their complete evaporation chain is also extracted. The set of data puts strong constraints on the behaviour of the level density (LD) of light nuclei above the threshold for particle emission. In particular, a fast increase of the LD parameter with excitation energy is supported by the data. Residual deviations from a statistical behaviour are seen in two specific channels, and tentatively associated with a contamination from direct reactions and/or α-clustering effects. These channels are studied in further details in the second paper of the series.

\alpha-clustering effects in dissipative 12C+12C reactions at 95 MeV

Dissipative 12C+12C reactions at 95 MeV are fully detected in charge with the GARFIELD and RCo apparatuses at LNL. A comparison to a dedicated Hauser-Feshbach calculation allows to select events which correspond, to a large extent, to the statistical evaporation of highly excited 24Mg, as well as to extract information on the isotopic distribution of the evaporation residues in coincidence with their complete evaporation chain. Residual deviations from a statistical behaviour are observed in \alpha yields and attributed to the persistence of cluster correlations well above the 24Mg threshold for 6 \alphas decay.

In vitro γ-ray-induced inflammatory response is dominated by culturing conditions rather than radiation exposures

The inflammatory pathway has a pivotal role in regulating the fate and functions of cells after a wide range of stimuli, including ionizing radiation. However, the molecular mechanisms governing such responses have not been completely elucidated yet. In particular, the complex activation dynamics of the Nuclear transcription Factor kB (NF-kB), the key molecule governing the inflammatory pathway, still lacks a complete characterization. In this work we focused on the activation dynamics of the NF-kB (subunit p65) pathway following different stimuli. Quantitative measurements of NF-kB were performed and results interpreted within a systems theory approach, based on the negative feedback loop feature of this pathway. Time-series data of nuclear NF-kB concentration showed no evidence of γ-ray induced activation of the pathway for doses up to 5Gy but highlighted important transient effects of common environmental stress (e.g. CO2, temperature) and laboratory procedures, e.g. replacing the culture medium, which dominate the in vitro inflammatory response.

The ANDANTE project: a multidisciplinary approach to neutron RBE.

UNLABELLED The usual method for estimating the risk from exposure to neutrons uses the concept of relative biological effectiveness (RBE) compared with the risk from photons, which is better known. RBE has been evaluated using cellular and animal models. But this causes difficulties in applying the concept to humans. The ANDANTE project takes a new approach using three different disciplines in parallel: Physics: a track structure model is used to contrast the patterns of damage to cellular macro-molecules from neutrons compared with photons. The simulations reproduce the same energy spectra as are used in the other two approaches. Stem cell radiobiology: stem cells from thyroid, salivary gland and breast tissue are given well characterised exposures to neutrons and photons. A number of endpoints are used to estimate the relative risk of damage from neutrons compared with photons. Irradiated cells will also be transplanted into mice to investigate the progression of the initial radiation effects in stem cells into tumours in a physiological environment. EPIDEMIOLOGY the relative incidence rates of second cancers of the thyroid, salivary gland and breast following paediatric radiotherapy (conventional radiotherapy for photons and proton therapy for neutrons) are investigated in a pilot single-institution study, exploring the possible design of a multi-institution prospective study comparing the long-term out-of-field and in-field effects of scanned and scattered protons. The results will be used to validate an RBE-based risk model developed by the project, and validate the corresponding RBE values.

The COOLER Code: A Novel Analytical Approach to Calculate Subcellular Energy Deposition by Internal Electron Emitters

COmputation Of Local Electron Release (COOLER), a software program has been designed for dosimetry assessment at the cellular/subcellular scale, with a given distribution of administered low-energy electron-emitting radionuclides in cellular compartments, which remains a critical step in risk/benefit analysis for advancements in internal radiotherapy. The software is intended to overcome the main limitations of the medical internal radiation dose (MIRD) formalism for calculations of cellular S-values (i.e., dose to a target region in the cell per decay in a given source region), namely, the use of the continuous slowing down approximation (CSDA) and the assumption of a spherical cell geometry. To this aim, we developed an analytical approach, entrusted to a MATLAB-based program, using as input simulated data for electron spatial energy deposition directly derived from full Monte Carlo track structure calculations with PARTRAC. Results from PARTRAC calculations on electron range, stopping power and residual energy versus traveled distance curves are presented and, when useful for implementation in COOLER, analytical fit functions are given. Example configurations for cells in different culture conditions (V79 cells in suspension or adherent culture) with realistic geometrical parameters are implemented for use in the tool. Finally, cellular S-value predictions by the newly developed code are presented for different cellular geometries and activity distributions (uniform activity in the nucleus, in the entire cell or on the cell surface), validated against full Monte Carlo calculations with PARTRAC, and compared to MIRD standards, as well as results based on different track structure calculations (Geant4-DNA). The largest discrepancies between COOLER and MIRD predictions were generally found for electrons between 25 and 30 keV, where the magnitude of disagreement in S-values can vary from 50 to 100%, depending on the activity distribution. In calculations for activity distribution on the cell surface, MIRD predictions appeared to fail the most. The proposed method is suitable for Auger-cascade electrons, but can be extended to any energy of interest and to beta spectra; as an example, the 3H case is also discussed. COOLER is intended to be accessible to everyone (preclinical and clinical researchers included), and may provide important information for the selection of radionuclides, the interpretation of radiobiological or preclinical results, and the general establishment of doses in any scenario, e.g., with cultured cells in the laboratory or with therapeutic or diagnostic applications. The software will be made available for download from the DTU-Nutech website: http://www.nutech.dtu.dk/.