Biophysik

A new physical module for the biophysical simulation code PARTRAC has recently been developed, based on newly derived electron inelastic-scattering cross-sections in liquid water. In the present work, two modules of PARTRAC describing the production, diffusion and interaction of chemical species were developed with the specific purpose of quantifying the role of the uncertainties in the parameters controlling the early stages of liquid water radiolysis. A set of values for such parameters was identified, and time-dependent yields and frequency distributions of chemical species produced by electrons of different energies were calculated. The calculated yields were in good agreement with available data and simulations, thus confirming the reliability of the code. As the primary-electron energy decreases down to 1 keV, the ·OH decay kinetics were found to get faster, reflecting variations in the spatial distribution of the initial energy depositions. In agreement with analogous works, an opposite trend was found for energies of a few hundred eV, due to the very small number of species involved. The spreading effects shown at long times by ·OH frequency distributions following 1 keV irradiation were found to be essentially due to stochastic aspects of the chemical stage, whereas for 1 MeV tracks the physical and pre-chemical stages also were found to play a significant role. Relevant differences in the calculated eaq– yields were found by coupling the physics of PARTRAC with descriptions of the pre-chemical and chemical stages adopted in different models. This indicates a strict interrelation of the various stages, and thus a strong dependence of the parameter values on the assumptions made for the preceding and subsequent stages of the process. Although equally acceptable results can be obtained starting from different assumptions, it is necessary to keep control of such uncertainties, since they can significantly influence the modeling of radical attack on DNA and, more generally, radiobiological damage estimation. This study confirms the need for new, independently derived data on specific steps of water radiolysis, to be included in comprehensive biophysical simulation codes.

Radiation-induced adaptive response belongs to the group of non-targeted effects that do not require direct exposure of the cell nucleus by radiation. It is described as the reduced damaging effect of a challenging radiation dose when induced by a previous low priming dose. Adaptive responses have been observed in vitro and in vivo using various indicators of cellular damage, such as cell lethality, chromosomal aberrations, mutation induction, radiosensitivity, and DNA repair. Adaptive response can be divided into three successive biological phenomena, the intracellular response, the extracellular signal, and the maintenance. The intracellular response leading to adaptation of a single cell is a complex biological process including induction or suppression of gene groups. An extracellular signal, the nature of which is unknown, may be sent by the affected cell to neighbouring cells causing them to adapt as well. This occurs either by a release of diffusible signalling molecules or by gap-junction intercellular communication. Adaptive response can be maintained for periods ranging from of a few hours to several months. Constantly increased levels of reactive oxygen species (ROS) or nitric oxide (NO) have been observed in adapted cells and both factors may play a role in the maintenance process. Although adaptive response seems to function by an on/off principle, it is a phenomenon showing a high degree of inter- and intraindividual variability. It remains to be seen to what extent adaptive response is functional in humans at relevant dose and dose-rate exposures. A better understanding of adaptive response and other non-targeted effects is needed before they can be confirmed as risk estimate factors for the human population at low levels of ionising radiation.

The average or amorphous track model uses the response of a system to gamma-rays and the radial distribution of dose about an ion’s path to describe survival and other cellular endpoints from proton, heavy ion, and neutron irradiation. This model has been used for over 30 years to successfully fit many radiobiology data sets. We review several extensions of this approach that address objections to the original model, and consider applications of interest in radiobiology and space radiation risk assessment. In the light of present views of important cellular targets, the role of target size as manifested through the relative contributions from ion-kill (intra-track) and gamma-kill (inter-track) remains a critical question in understanding the success of the amorphous track model. Several variations of the amorphous model are discussed, including ones that consider the radial distribution of event-sizes rather than average electron dose, damage clusters rather than multiple targets, and a role for repair or damage processing.

Radiation protection is a topic of great public concern and of many scientific investigations, because ionizing radiation is an established risk factor for leukaemia and many solid tumours. Exposure of the public to ionizing radiation includes exposure to background radiation, as well as medical and occupational exposures. A large fraction of the exposure from diagnostic procedures comes from medical imaging. Computed tomography (CT) is the major single contributor of diagnostic radiation exposure. An increase in the use of CTs has been reported over the last decades in many countries. Children have smaller bodies and lower shielding capacities, factors that affect the individual organ doses due to medical imaging. Several risk models have been applied to estimate the cancer burden caused by ionizing radiation from CT. All models predict higher risks for cancer among children exposed to CT as compared to adults. However, the cancer risk associated with CT has not been assessed direc...

GATE/GEANT is a Monte Carlo code dedicated to nuclear medicine that allows calculation of the dose to organs of voxel phantoms. On the other hand, MIRD is a well-developed system for estimation of the dose to human organs. In this study, results obtained from GATE/GEANT using Snyder phantom are compared to published MIRD data. For this, the mathematical Snyder phantom was discretized and converted to a digital phantom of 100 × 200 × 360 voxels. The activity was considered uniformly distributed within kidneys, liver, lungs, pancreas, spleen, and adrenals. The GATE/GEANT Monte Carlo code was used to calculate the dose to the organs of the phantom from mono-energetic photons of 10, 15, 20, 30, 50, 100, 200, 500, and 1000 keV. The dose was converted into specific absorbed fraction (SAF) and the results were compared to the corresponding published MIRD data. On average, there was a good correlation (r 2>0.99) between the two series of data. However, the GATE/GEANT data were on average −0.16 ± 6.22% lower than the corresponding MIRD data for self-absorption. Self-absorption in the lungs was considerably higher in the MIRD compared to the GATE/GEANT data, for photon energies of 10–20 keV. As for cross-irradiation to other organs, the GATE/GEANT data were on average +1.5 ± 8.1% higher than the MIRD data, for photon energies of 50–1000 keV. For photon energies of 10–30 keV, the relative difference was +7.5 ± 67%. It turned out that the agreement between the GATE/GEANT and the MIRD data depended upon absolute SAF values and photon energy. For 10–30 keV photons, where the absolute SAF values were small, the uncertainty was high and the effect of cross-section prominent, and there was no agreement between the GATE/GEANT results and the MIRD data. However, for photons of 50–1,000 keV, the bias was negligible and the agreement was acceptable.

Exposure to space radiation has long been acknowledged as a potential showstopper for long-duration manned interplanetary missions. In an effort to gain more information on space radiation risk and to develop countermeasures, NASA initiated several years ago a Space Radiation Health Program, which is currently supporting biological experiments performed at the Brookhaven National Laboratory. Accelerator-based radiobiology research in the field of space radiation research is also under way in Russia and Japan. The European Space Agency (ESA) supports research in the field in three main directions: spaceflight experiments on the International Space Station; modeling and simulations of the space radiation environment and transport; and, recently, ground-based radiobiology experiments exploiting the high-energy SIS18 synchrotron at GSI in Germany (IBER program). Several experiments are currently under way within IBER, and so far, beams of C and Fe-ions at energies between 11 and 1,000 MeV/n have been used in cell and tissue targets.

Radiobiological archives have not been overwhelmed by applications to use their stored tissue materials, in part because of lack of technologies to conduct quantitative analysis of the tissues. Over the last decade, advances in methodology have made it possible to routinely extract both DNA and RNA from archival materials. The quantitative analysis of gene expression by reverse transcription real-time PCR (QRT-PCR), and of gene copy number by array-based CGH (aCGH), are now firmly established methods for the study of tissue samples stored as paraffin blocks. More recent developments in proteomic technology have enabled the extraction of proteins from formalin-fixed paraffin-embedded (FFPE) tissue samples. These protein extracts have been used to produce quantitative data by Western blotting and even to identify proteins through LC/MS analysis. The development of applications using gel-based proteomics (2D/MS) is still a future challenge. This report gives an overview of the methodology already applicable on FFPE tissue, as well as the novel technologies to be used in the future research. Our goal is to collect existing animal and human tissue samples for use by the radiation biology community, to test new technologies for preparation of material from tissue samples, and to actively pursue materials arising from ongoing research.