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Different from conventional radiotherapy (CONV-RT), FLASH radiotherapy (FLASH-RT) delivers a single high dose at a mean dose rate ≥40 ​Gy/s in milliseconds to achieve similar tumor control to CONV-RT while sparing normal tissues from detrimental injury. It provides an intriguing perspective in improving clinical outcomes for tumor patients as well as a novel way to enhance the differential responses between normal and tumor tissues. However, its mechanisms remain largely unclear. In this paper, we review the currently available publications on FLASH-RT and parse the probable mechanisms of three major aspects including the production of reactive oxygen species, DNA damage response, and immunoreaction. Experiments specifically designed to disclose the intrinsic difference between normal and malignant cells in response to FLASH-RT and CONV-RT are necessary to prove these hypotheses.

Linear Energy Transfer (LET) is widely used to express the radiation quality of ion beams, when characterizing the biological effectiveness. However, averaged LET may be defined in multiple ways, and the chosen definition may impact the resulting reported value. We review averaged LET definitions found in the literature, and quantify which impact using these various definitions have for different reference setups. We recorded the averaged LET definitions used in 354 publications quantifying the relative biological effectiveness (RBE) of hadronic beams, and investigated how these various definitions impact the reported averaged LET using a Monte Carlo particle transport code. We find that the kind of averaged LET being applied is, generally, poorly defined. Some definitions of averaged LET may influence the reported averaged LET values up to an order of magnitude. For publications involving protons, most applied dose averaged LET when reporting RBE. The absence of what target medium is used and what secondary particles are included further contributes to an ill-defined averaged LET. We also found evidence of inconsistent usage of averaged LET definitions when deriving LET-based RBE models. To conclude, due to commonly ill-defined averaged LET and to the inherent problems of LET-based RBE models, averaged LET may only be used as a coarse indicator of radiation quality. We propose a more rigorous way of reporting LET values, and suggest that ideally the entire particle fluence spectra should be recorded and provided for future RBE studies, from which any type of averaged LET (or other quantities) may be inferred.

Objectives To derive conversions of antiquated exposure data into modern equivalents and to apply these in the assessment of the skin dose of pelvic radiographs since 1896. Methods The literature 1896–2018 was searched for implicit and explicit dose information. The early implicit dose data contained now obsolete descriptions of radiation quality and quantity for long since disappeared X-ray systems of limited efficiency. Converting the old information into modern specifications was achieved using contemporary data and computer simulations. Final dose calculations were done with modern software. Explicit radiation doses of later date reported in old quantities and units were adapted according to current recommendations. Results For the period before 1927 conversion algorithms for spark gap data and penetrometer hardnesses to high voltage could be derived. Electrical and X-ray efficiencies of several old röntgen systems were determined. Together they allowed reconstruction of 53 doses. After 1927 doses were generally explicitly specified; 114 were retrieved. Although an enormous spread was observed, the average skin dose was reduced by a factor of about 400. Conclusions Antiquated exposure data were successfully used for dose reconstruction. Extreme dose variability was a constant. Efforts to cut down doses were effective as skin doses went down from sub-erythema values to about one milligray. Electronic supplementary material The online version of this article (10.1186/s13244-019-0710-1) contains supplementary material, which is available to authorized users.

Purpose. Estimating the cancer risk associated with interplanetary travel is complicated by the lack of data for human exposure to high atomic number, high-energy (HZE) radiation encountered in space. Therefore, human exposure data from low linear energy transfer (low-LET) γ-ray radiation is used in cancer risk models with the critical assumption that HZE and γ-ray radiation have comparable biological effects, including the induction of the same spectrum of tumors with similar lethality. Recently this assumption has been challenged by several reports indicating that HZE radiation might produce more aggressive tumors. The goal of this research is to test the hypothesis that high-LET HZE radiation induced tumors are more aggressive than those that arise spontaneously or from exposure to low-LET γ-rays. Materials & methods. The FVB/N-Tg(MMTV-PyMT) and (DBAxFVB)F1-Tg(MMTV-PyMT) murine models of mammary cancer and the C3H-Tg(Afp-mCherry) and C3B6F1-Tg(Afp-mCherry) liver cancer models were used to determine the impact of exposure to 0.2 Gy of HZE 300 MeV/n silicon ions in comparison to 3 Gy of γ-rays and no radiation. Various measures of tumor aggressiveness including latency, size, pathological grade, prognostic biomarkers, metastasis, and survival were assessed. Results. For both mammary cancer models, there was no significant change in the latency of mammary tumors or in the number or size of pulmonary metastasis in silicon-irradiated mice compared to their sham-irradiated controls. For the C3H-Tg and C3B6-Tg liver cancer models, we did observe an increase in the incidence of liver cancer in irradiated mice, but no differences in measures of aggressiveness, including tumor size, grade, metastasis, or overall survival. Conclusion. The principle finding of our study is that tumors in the HZE-irradiated mice were not more aggressive than those arising from exposure to low-LET γ-rays or spontaneously. Thus, we conclude that enhanced aggressiveness does not appear to be a uniform characteristic of all tumors in HZE-irradiated animals.

The relation of radiation exposure (dose) with acute radiation syndrome (ARS) depends on many factors. In this overview, we reconsider (1) radiation exposure characteristics (e.g. radiation quality, fractionation, dose rate, partial/total body irradiation) and (2) biological processes (e.g. radiosensitivity, cell cycle dependency, oxygenation) affecting acute health effects after exposure. Furthermore we include evidence from recently published work that examined the relationship of absorbed dose and risk of clinically relevant ARS in persons exposed after a radiation accident. We introduce the concept of radiation-related bioindicators for effect prediction. Bioindicators are considered here to be factors that integrate multiple radiation exposure characteristics and cell- and molecular-based processes to improve clinical prediction in persons with ARS.

Biological effectiveness of a certain absorbed dose of ionizing radiation depends on the radiation quality, i. e. the spectrum of ionizing particles and their energy distribution. As has been shown in several studies, the biological effectiveness is related to the pattern of energy deposits on the microscopic scale, the so-called track structure. Clusters of lesions in the DNA molecule within site sizes of few nanometers play a particular role in this context. This work presents a brief overview of nanodosimetric approaches to relate biological effects with track structure derived quantities and experimental techniques to derive such quantities.

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.

Results from archived (1986 and 1996) experiments were used to establish a baboon radiation-quality dose–response database with haematology biomarker time-course data following exposure to mixed-fields (i.e. neutron to gamma ratio: 5.5; dose: 0–8 Gy) and 60Co gamma-ray exposures (0–15 Gy). Time-course (i.e. 0–40 d) haematology changes for relevant blood-cell types for both mixed-field (neutron to gamma ratio = 5.5) and gamma ray alone were compared and models developed that showed significant differences using the maximum likehood ratio test. A consensus METREPOL-like haematology ARS (H-ARS) severity scoring system for baboons was established using these results. The data for mixed-field and the gamma only cohorts appeared similar, and so the cohorts were pooled into a single consensus H-ARS severity scoring system. These findings provide proof-of-concept for the use of a METREPOL H-ARS severity scoring system following mixed-field and gamma exposures.

Deep underground laboratories (DULs) were originally created to host particle, astroparticle or nuclear physics experiments requiring a low-background environment with vastly reduced levels of cosmic-ray particle interference. More recently, the range of science projects requiring an underground experiment site has greatly expanded, thus leading to the recognition of DULs as truly multidisciplinary science sites that host important studies in several fields, including geology, geophysics, climate and environmental sciences, technology/instrumentation development and biology. So far, underground biology experiments are ongoing or planned in a few of the currently operating DULs. Among these DULs is the Gran Sasso National Laboratory (LNGS), where the majority of radiobiological data have been collected. Here we provide a summary of the current scenario of DULs around the world, as well as the specific features of the LNGS and a summary of the results we obtained so far, together with other findings collected in different underground laboratories. In particular, we focus on the recent results from our studies of Drosophila melanogaster, which provide the first evidence of the influence of the radiation environment on life span, fertility and response to genotoxic stress at the organism level. Given the increasing interest in this field and the establishment of new projects, it is possible that in the near future more DULs will serve as sites of radiobiology experiments, thus providing further relevant biological information at extremely low-dose-rate radiation. Underground experiments can be nicely complemented with above-ground studies at increasing dose rate. A systematic study performed in different exposure scenarios provides a potential opportunity to address important radiation protection questions, such as the dose/dose-rate relationship for cancer and non-cancer risk, the possible existence of dose/dose-rate threshold(s) for different biological systems and/or end points and the possible role of radiation quality in triggering the biological response.

An attempt towards an experimental set up which could provide the experimental data on correlation processes occurred simultaneously in two distanced DNA targets within a charged particle track is presented. A modified Jet Counter nanodosemeter was used in two experiments with carbon ions with mean energies of 52 and 23 MeV. The probability distributions of the correlated pairs of ionisation clusters produced in two neighbouring sensitive volumes are presented. A question of potential new descriptors of radiation quality is raised.

In the past two decades, a body of experimental evidences in vitro has shown the presence of a plethora of phenomena occurring after low-dose irradiation [including hypersensitivity and induced radioresistance (IRR), adaptive response, bystander effect (BE) and genomic instability], which might imply a non-linear behaviour of cancer risk curves in the low-dose region and question the validity of the linear no-threshold model for cancer risk assessment in such a dose region. In this framework, a systematic investigation have been undertaken on non-linear effects at low doses as a function of different radiation quality and cellular radiosensitivity and in terms of different biological end points. The present article reports the recent results on hyper-radiosensitivity and IRR and BE phenomena, in terms of clonogenic survival in V79 Chinese hamster cells and T98G human glioblastoma cells irradiated with protons and carbon ions with different energy, as a function of dose (and fluence).

The magnitude of the spread in specific energy deposition per cell may be a confounding factor in dose-response analysis motivating derivation of explicit data for the most common brachytherapy isotopes (125)I and (192)Ir, and for (60)Co radiation frequently used as reference in RBE studies. The aim of this study is to analyse the microdosimetric spread as given by the frequency distribution of specific energy for a range of doses imparted by (125)I, (192)Ir and (60)Co sources. An upgraded version of the Monte Carlo code PENELOPE was used for scoring energy deposition distributions in liquid water for each of the radiation qualities. Frequency distributions of specific energy were calculated according to the formalism of Kellerer and Chmelevsky. Results indicate that the magnitude of the microdosimetric spread increases with decreasing target size and decreasing energy of the radiation quality. Within the clinical relevant dose range (1 to 100 Gy), the spread does not exceed 4 % for (60)Co, 5 % for (192)Ir and 6 % for (125)I. The frequency distributions can be accurately approximated with symmetrical normal distributions at doses down to 0.2 Gy for (60)Co, 0.1 Gy for (192)Ir and 0.08 Gy for (125)I.

Microdosimetry is the study and application of the microscopic features and stochastics of ionising radiations that cannot be described by the average macroscopic quantity absorbed dose. Microdosimetry is intimately related to radiation quality, but it also encompasses the inhomogeneities of interactions and energy depositions within a single radiation type. A variety of past and current approaches will be summarised and some examples given of implications to radiation protection and medicine, as well as to basic mechanistic studies of radiation effects.

The present investigation aimed to characterise the shape of dose-response curve and determining the frequency distribution of various aberration types as a function of dose and radiation quality in AG01522 primary human fibroblasts in the 0.1- to 1-Gy dose range. For this purpose, the cells were irradiated with 7.7 and 28.5 keV µm(-1) low-energy protons, 62 keV µm(-1 4)He(2+) ions (LNL Radiobiology facility) or X rays and samples collected for 24-colour mFISH analysis. X rays and 7.7 keV µm(-1) protons displayed a quadratic dose-response curve solely for total and simple exchanges, whereas for high-linear energy transfer radiations, a linear dose-response curve was observed for all the aberration categories, with the exception of complex exchanges.

The yield of chromosome aberrations is not only dependent on dose but also on radiation quality, with high linear energy transfer (LET) typically having a greater biological effectiveness per unit dose than those of low-LET radiation. Differences in radiation track structure and cell morphology can also lead to quantitative differences in the spectra of the resulting chromosomal rearrangements, especially at low doses associated with typical human exposures. The development of combinatorial fluorescent labelling techniques (such as mFISH and mBAND) has helped to reveal the complexity of rearrangements, showing increasing complexity of observed rearrangements with increasing LET but has a resolution limited to ∼10 MBp. High-LET particles have not only been shown to produce clustered sites of DNA damage but also produce multiple correlated breaks along its path resulting in DNA fragments smaller than the resolution of these techniques. Additionally, studies have shown that the vast majority of radiation-induced HPRT mutations were also not detectable using fluorescent in situ hybridisation (FISH) techniques, with correlation of breaks along the track being reflected in the complexity of mutations, with intra- and inter-chromosomal insertions, and inversions occurring at the sites of some of the deletions. Therefore, the analysis of visible chromosomal rearrangements observed using current FISH techniques is likely to represent just the tip of the iceberg, considerably underestimating the extent and complexity of radiation induced rearrangements.

Recombination chambers are linear energy transfer (LET)-dependent detectors and their applications are closely related to the problem of estimating radiation quality. The operational principle is based on the phenomenon of the initial recombination of ions in gases. Practical usefulness of the chambers is well confirmed by experimental results, however, the correlation of the response with LET is based on an approximated theoretical description of initial recombination of ions in gases. In this work, a precise numerical model of the REM-2 recombination chamber has been prepared, in order to calculate the dose distributions versus LET inside the chamber. The results form a set of data for further validation of recombination methods.

The biological action of ionizing charged particles is initiated at the DNA level, and the effectiveness with which the initial physical effect changes into measurable biological damage is likely ruled by the stochastics of ionizations produced by the incident ions in subcellular nanometric volumes. Based on this hypothesis, experimental nanodosimetry aims at establishing a new concept of radiation quality that builds on measurable characteristics of the particle track structure at the nanometer scale. Three different nanodosimetric detection systems have been developed to date that allow measurements of the number of ionizations produced by the passage of a primary particle in a nanometer-size gas volume (in unit density scale). Within the Italian project MITRA (MIcrodosimetry and TRAck structure), funded by the Italian Istituto Nazionale di Fisica Nucleare (INFN) and the EMRP Joint Research Project 'BioQuaRT' (Biologically Weighted Quantities in Radiotherapy), experiments have been carried out, in which the frequency distribution of ionizations produced by proton and carbon ion beams of given energy was measured with the three nanodosimetric detectors. Descriptors of the track structure can be derived from these distributions. In particular, the first moment M1, representing the mean number of ionizations produced in the target volume, and the cumulative probability Fk of measuring a number ν ≥ k of ionizations. The correlation between measured nanodosimetric quantities and experimental radiobiological data available in the literature is here presented and discussed.

Low-linear energy transfer (low-LET) γ-ray exposure is a risk factor for colorectal cancer (CRC). Due to their high-LET nature, energetic iron ions found in space are expected to pose greater CRC risks to astronauts undertaking long-duration space missions beyond low Earth orbit. Wild-type p53-induced phosphatase 1 (Wip1) is important for cellular DNA damage response and its abrogation has been shown to inhibit spontaneous intestinal tumorigenesis in APC(Min/+) mice, a well-studied mouse model of human CRC. However, the relationship of Wip1 to radiation-induced intestinal tumorigenesis, especially by energetic iron ions, has not been investigated in APC(Min/+) mice. We have previously reported that there is a greater intestinal tumorigenic potential of iron-ion radiation relative to (137)Cs γ rays, so the purpose of the current study was to investigate whether Wip1 abrogation could influence high-LET dependent intestinal tumorigenesis in APC(Min/+) mice. Intestinal tumor frequency and grade were assessed in APC(Min/+)/Wip1(-/-) mice and results were compared to those in APC(Min/+)/Wip1(+/+) mice after exposure to a mean absorbed dose of 2 Gy from (137)Cs γ rays or 1.6 Gy from 1 GeV/n iron ions. Cellular differentiation and proliferation were also assessed in the intestinal tumors of sham-irradiated and irradiated mice. Decreased tumor frequency and lower tumor grade were observed in APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice. Notably, a similar decrease (∼6-fold in both groups) in tumor number was observed in sham-irradiated and γ-irradiated APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice. However, tumorigenesis in the energetic iron-ion exposed group was reduced ∼8-fold in APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice. A significantly lower proliferation/differentiation index in tumors of iron-ion exposed APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice suggests that reduced proliferation and enhanced differentiation as a result of Wip1 abrogation maybe involved. In conclusion, the current study demonstrated that the absence of Wip1 blocked radiation-induced intestinal tumorigenesis irrespective of radiation quality and has implications for developing preventive strategies against the tumorigenic potential of radiation exposure on earth and in outer space.

Purpose: Converting the measurable quantities to patient organ doses in projection radiography is usually based on a standard-sized patient model and a specific radiation quality, which are likely to differ from the real situation. Large inaccuracies can therefore be obtained in organ doses, because organ doses are dependent on the exposure parameters, exposure geometry and patient anatomy. In this study, the effect of radiation quality and patient thickness on the organ dose conversion factors were determined. Methods: In this study, the posterior-anterior projection radiograph of the thorax was selected in order to determine the effect of radiation quality (tube voltages of 70-130 kV and total filtrations of 3 mmAl to 4 mmAl + 0.2 mmCu) and patient thickness (anterior-posterior thicknesses of 19.4-30.8 cm) on the breast and lung dose conversion factors. For this purpose, Monte Carlo simulation programs ImpactMC and PCXMC were used with computed tomography examination data of adult male and female patients and mathematical hermaphrodite phantoms, respectively. Results: Compared to the reference beam quality and patient thickness, the relative variation range in organ dose conversion factors was up to 74% for different radiation qualities and 122% for different patient thicknesses. Conclusions: Conversion factors should only be used with comprehensive understanding of the exposure conditions, considering the exposure parameters, exposure geometry and patient anatomy they are valid for. This study demonstrates that patient thickness-specific and radiation quality-specific conversion factors are needed in projection radiography. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

The accumulated evidence in the literature indicates that a cluster of two or more lesions within one or two helical turns of the DNA is more challenging to repair than individual, widely dispersed lesions. The biological importance of clustered DNA lesions, especially complex double-strand breaks (DSB) and some types of non-DSB clusters (e.g., opposed bases that are oxidized), are now well known within the radiation research community. Still, many details of the induction and biological processing of complex clusters remain to be elucidated, especially in human cells. In this mini-review, we discuss recent advances in our understanding of the pathway(s) used by the mammalian cells to process and efficiently repair complex clusters other than the DSB. The effects of radiation quality and hypoxia on cluster induction and complexity are also briefly reviewed and discussed. Additional research is needed to better understand and quantify the multi-scale physiochemical and biological processes ultimately responsible for radiation-induced mutagenesis and genomic instability. New information and models to better quantify intermediate events (outcomes) related to the biological processing of non-DSB clusters are also important for ongoing efforts to assess the human health risks of terrestrial and space radiation environments and to guide the radiation therapy treatment planning process, especially for protons and carbon ions.

In a previous study, microdosimetric simulations were performed for tritium uniformly distributed in a medium, and for tritium bound to biologically critical sites of dimensions from 10 nm to 2 µm. Results of local energy density, i.e. energy deposition in microscopic regions, are different for these two cases. Based on the spatial distribution of energy deposition, dose mean lineal energies are calculated for tritium in the forms of tritiated water (HTO) and organically bound tritium (OBT). The dose mean lineal energies of OBT are about a factor of 1.7 higher than those of HTO in a wide range of target dimensions of biological interest. The results are consistent with radiobiological findings that OBT is about twice as effective as HTO. In this study, the same calculations were performed for (60)Co gamma rays in a wide range of target dimensions of biological interest (10 nm to 2 µm). Compared with (60)Co gamma rays, the estimated relative biological effectiveness could vary from 1.3 to 3.5 for HTO, and 2.3 to 5.6 for OBT. The results are consistent with radiobiological findings for various biological endpoints in different biological systems that OBT is about twice as effective as HTO.

The Active personal dosemeter (APD) developed by Cekmece Nuclear Research and Training Center/Nuclear Electronic Laboratory (CNRTC/NEL) was calibrated at the reference radiation quality (137Cs). The performance tests were carried out with 137Cs, 60Co and X-ray beam qualities in compliance with the standards of International Organization for Standardization ISO4037-1,3 and The International Electrotechnical Commission, IEC61526:2010. Response of the personal dose equivalent was observed to be within the range from -7.6% to +4.2%. The dose equivalent rates were observed with the maximum deviation -26.8% for 0.1 mSv h-1 and within the range from -2.3% to +10.1% for dose rates over 0.5 mSv h-1. It is found that the APDs have lower readings up to 50% for 33 keV photons and perform a distribution in the acceptable limits for over 33 keV. Angular dependence was tested at 0°, ±30° and ±60° in orthogonal plane and the angular dependence of the APDs is within acceptable limits except N40.

The aim of this paper is the characterization of four thermoluminescence detectors (TLD), namely, LiF:Mg,Ti, LiF:Mg,Cu,P, Li2B4O7:Mn and Li2B4O7:Cu for the measurement of the entrance surface air kerma (ESAK) and estimation of the mean glandular dose (MGD) in digital mammography examinations at hospitals and clinics. Low-energy x-ray beams in the typical energy ranges of mammography, produced with a tungsten target and additional 60 µm molybdenum filtration were implemented and characterized at the Laboratory of Metrology of Ionizing Radiation at Instituto Superior Tecnico. These beams were used for the characterization of the TLDs in terms of sensitivity, linearity, reproducibility, energy dependence and fading at 40 °C. The energy dependence test was further extended using clinical beams produced by mammography units at hospitals and clinics. The method proposed by the International Atomic Energy Agency was used for the measurement of ESAK and assessment of MGD. The combined standard uncertainty for the measurement of ESAK (and MGD) was determined in accordance to the Guide to the expression of uncertainty in measurement. The x-ray beams generated in the 23-40 kVp range presented HVL values from 0.36 to 0.46 mm Al. The beam produced at 28 kVp (HVL 0.39 mm Al) was considered as reference. The radiation field defined a circle with 84 mm diameter with a maximum variation of the beam intensity of less than 1% at the top flat (plateau) within 4 cm of the central axis. The estimated total uncertainty for the measurement of air kerma was 0.42%. All the TL detectors tested showed good performance except the commercial Li2B4O7:Mn (or TLD-800) which was excluded due to its poor sensitivity in our experimental set up. Both lithium fluorides showed better linearity and reproducibility as well as lower energy dependence and fading when compared to lithium borates. The stable behaviour of LiF:Mg,Ti and LiF:Mg,Cu,P detectors is reflected in the low combined standard uncertainty of ±5.6% and ±4.3% respectively (or ±5.1% and ±3.6% if fading is neglected). In general a total combined uncertainty lower than ±10% for the measurement of ESAK was obtained for the four TL materials studied.

The European Dosimetry Group (EURADOS) first started performing international intercomparisons for whole-body dosemeters for individual monitoring services in 1998. Since 2008, these whole-body intercomparisons have been performed on a regular basis. In this latest intercomparison (IC2014), 96 monitoring services from 35 countries (mostly European) participated with 112 dosimetry systems. Unlike in the previous intercomparisons, the whole registration, communication and data exchange process was handled by a new on-line platform. All dosemeter irradiations were carried out in the Seibersdorf accredited dosimetry laboratory. The irradiation plan consisted of nine irradiation setups with five different photon radiation qualities (S-Cs, S-Co, RQR7, W-80 and W-150) and two different angles of radiation incidence (0° and 60°). The paper describes and analyses the individual results for the personal dose equivalent quantities Hp(10) and if requested, Hp(0.07), for all participating systems and compares these results with the ISO 14146 'trumpet curve' performance criteria. The results show that 100 systems (89 % of all systems) do fulfil the general ISO 14146 performance criteria. This paper gives an overview on the performance of the participating individual monitoring services and the influence of the dosemeter type on the observed response values.

Three types of Gafchromic films have been studied to investigate their potential for use as a visually readable dosemeter for persons acting as first responders in connection with radiological or nuclear emergencies. The two most sensitive film types show a pronounced variation in sensitivity by photon energy and are therefore not suitable for use in cases of unknown exposures. The third film type tested (RTQA2), which is intended for quality control in radiation therapy has a sensitivity that is independent of the radiation quality, and is therefore considered as the most optimal for visual reading in situ. Tests carried out on a group of 10 human observers showed that absorbed doses down to 40 mGy can be detected by the eye. Read by a portable densitometer, qualitative absorbed dose estimates down to 9 mGy can be achieved. The colour change is obtained instantaneously, giving first responders immediate information about the presence of beta-, gamma- and X-ray radiation.

This paper presents the results of an intercomparison for extremity dosemeters organised by the European radiation dosimetry group in 2009. In total, 59 systems were tested during this exercise including ring, stall and wrist dosemeters. A total of 1652 dosemeters were irradiated in the selected fields of photons and beta radiation qualities on appropriate phantoms (ISO finger and pillar phantom) in the dose quantity H(p)(0.07). All irradiations were carried out in selected accredited reference dosemetry laboratories (Seibersdorf Laboratories, Austria and IRSN, France). The results show that, especially at low-energy beta radiations ((85)Kr) and for beta irradiations with large angles of incidence (60°), many tested systems show pronounced under responses. On the other hand, for photon irradiations down to energies of 16 keV most systems showed good results. A participants meeting was held at IM2010 with discussion on both general aspects of this intercomparison and specific problems.

Most of the important biological effects associated with the exposure to ionizing radiations are mirrored at the chromosomal level. In all cases, changes in the levels of cytogenetic effects are associated with changes in absorbed dose, dose rate and radiation quality. Some of the complexities associated with the quantitative description of such changes in response can be circumvented by appealing to concepts embodied in what has been called the "mean inactivation dose". Additional metrics designed to provide LET-dependent "signatures" of damage have been employed with moderate degrees of success. These, along with some alternative approaches, are discussed in an effort to stimulate discussion, and to further work leading to a better understanding of mechanisms involved in the production and significance of chromosome aberrations after exposure to ionizing radiations.

The pixels in digital detectors used in x-ray imaging can be considered as small dose meters. In mammography, the image detector area is commonly only partly covered by tissue and the incident air kerma could be monitored by using pixel values from the detector elements in the unattenuated primary beam area. The measured air kerma could be used for patient dose estimation. The air kerma and radiation quality dependence of the response of pixel values within a large exposure range for two direct digital detector types was experimentally investigated for this purpose. Using these calibration results, air kerma was measured from clinical images and compared with tube output calculation. The differences between the two methods were typically below 2% and measurements based on pixel values can therefore be recommended.

To determine whether the physical differences between high- and low-LET radiation are reflected in the biological responses of exposed cells, we detailed phospho-protein profiles of three proteins functional in radiation repair and signal transduction. Detailing gamma-H2AX, pATF2 Ser490/498 and pSMC1 Ser957 kinetics after X-ray and iron-ion exposure also provides a window into understanding the underlying cellular responses. Phosphorylated forms of these proteins have been documented to co-localize at sites of double-strand breaks (DSBs) after low-LET radiation exposures, and two of these phosphorylations, pATF2 and pSMC1, are specifically dependent on ATM. Flow cytometry-based methods were used to quantify total levels of each phospho-protein at various times after irradiation. As expected, we observed a greater induction and persistence in gamma-H2AX after iron-ion (high-LET) exposure compared to X-ray (low-LET) exposure. In contrast, pATF2 and pSMC1 showed markedly lower induction levels after iron-ion exposure compared to equivalent doses of X rays. Quantification of pATF2 and pSMC1 foci revealed fewer cells containing foci and fewer foci per cell after iron-ion compared to X-ray exposure. These findings suggest that ATM responds to DSBs induced by high-LET radiation differently from DSBs induced by low-LET radiation.

In the framework of developing instrumentation aimed at measuring radiation quality, a new production of improved silicon microdosimeters based on the Monolithic Silicon Telescope (MST) technology has been recently finalized. Reduced dead layer, high fluence rate capability and better chord length distribution have been obtained thorough modified process and design. Electrical and functional tests have been successfully completed and are presented.

Ion-beam therapy faces a growing demand of tools able to map radiation quality within the irradiated volume. Although analytical computations and simulations provide useful estimations of dose and radiation quality, the direct measure of those parameters would improve ion-beam therapy in particular when deep-seated tumours are irradiated, tissue composition and density are variable or organs at risk are near the tumour. Several ion-beam therapy facilities are studying detectors and procedures for measuring the radiation quality on a microdosimetric as well as a nanodosimetric scale. Simplicity and miniaturisation of the devices are essential for measurements first in phantoms and thereafter during therapy, particularly for intra-cavity detectors. MedAustron is studying solid-state detectors based on a single crystal chemical vapour deposition diamond. In collaboration with Italian National Institute for Nuclear Physics (INFN), Tor Vergata and Legnaro; INFN-microdosimetry and track structure project; Austrian Institute of Technology, Vienna; and Italian National agency for new technologies, energy and sustainable economic development, Rome, prototypes have been developed to characterise radiation quality in sizes equivalent to one micrometre of biological tissue.

To investigate the dependence of the bystander cell-killing effect on radiation dose and quality, and to elucidate related molecular mechanisms.Normal human fibroblast WI-38 cells were irradiated with 0.125 - 2 Gy of γ-rays or carbon ions and were co-cultured with non-irradiated cells. Survival rates of bystander cells were investigated using the colony formation assays, and nitrite concentrations in the medium were measured using the modified Saltzman method.Survival rates of bystander cells decreased with doses of γ-rays and carbon ions of ≤ 0.5 Gy. Treatment of the specific nitric oxide (NO) radical scavenger prevented reductions in survival rates of bystander cells. Moreover, nitrite concentrations increased with doses of less than 0.25 Gy (γ-rays) and 1 Gy (carbon ions). The dose responses of increased nitrite concentrations as well as survival reduction were similar between γ-rays and carbon ions. In addition, negative relationships were observed between survival rates and nitrite concentrations.The bystander cell-killing effect mediated by NO radicals in normal human fibroblasts depends on irradiation doses of up to 0.5 Gy, but not on radiation quality. NO radical production appears to be an important determinant of γ-ray- and carbon-ion-induced bystander effects.

NASA has implemented new radiation quality factors (QFs) for projecting cancer risks from space radiation exposures to astronauts. The NASA QFs are based on particle track structure concepts with parameters derived from available radiobiology data, and NASA introduces distinct QFs for solid cancer and leukaemia risk estimates. The NASA model was reviewed by the US National Research Council and approved for use by NASA for risk assessment for International Space Station missions and trade studies of future exploration missions to Mars and other destinations. A key feature of the NASA QFs is to represent the uncertainty in the QF assessments and evaluate the importance of the QF uncertainty to overall uncertainties in cancer risk projections. In this article, the biophysical basis for the probability distribution functions representing QF uncertainties was reviewed, and approaches needed to reduce uncertainties were discussed.

MIDN (MIcroDosimetry iNstrument) is a payload on the MidSTAR-I spacecraft (Midshipman Space Technology Applications Research) under development at the United States Naval Academy. MIDN is a solid-state system being designed and constructed to measure microdosimetric spectra to determine radiation quality factors for space environments. Radiation is a critical threat to the health of astronauts and to the success of missions in low-Earth orbit and space exploration. The system will consist of three separate sensors, one external to the spacecraft, one internal and one embedded in polyethylene. Design goals are mass

The quality of different photon radiations in small and large receptors is assessed in terms of microdosimetry. Monte Carlo simulations are performed for the electrons released by photons. To represent the case of a small receptor, only electrons released by the non-degraded incident photons are tracked. For a large receptor, all electrons released in the complete degradation process are followed. Dose averaged values, y(D), of the lineal energy are derived from the simulated tracks for monoenergetic photons from 10 keV to 2 MeV. In microdosimetry, the dose mean lineal energy is the major parameter of radiation quality. The results demonstrate distinct differences in radiation quality between high-energy gamma rays and conventional X rays that are present not just in small cell samples but also in large receptors, such as the human body. The values of y(D) suggest that, for both small and large receptors, conventional X rays should be about twice as effective as gamma rays from 60Co.

Proton beams (62 Mev) are used by the Laboratori Nazionali del Sud of the Italian Institute of Nuclear Physics to treat eye melanoma tumours at the therapeutic facility called CATANA. A cylindrical slim tissue-equivalent proportional counter (TEPC) of 2.7 mm external diameter has been used to compare the radiation quality of two spread-out Bragg peaks (SOBP) at the CATANA proton beam.

The quality factor for x-rays, gamma rays and electrons assigned as one need to be revised. It is observed that as the energy decreases, mean lethal radiation dose (Do)decreases as well and become more potent. It is therefore proposed that radiation quality in biological systems should be assessed in the mitotic phase of the cell cycles. Furthermore, based on the mean lethal radiation dose within specific energy range, an appropriate quality factor of x-rays, gamma rays and electrons should be assigned.

Purpose: Numerous studies have implicated elevated second cancer risks as a result of radiation therapy. Our aim in this paper was to contribute to an understanding of the effects of radiation quality on second cancer risks. In particular, we developed a biologically motivated model to study the effects of linear energy transfer (LET) of charged particles (including protons, alpha particles and heavy ions Carbon and Neon) on the risk of second cancer.A widely used approach to estimate the risk uses the so-called initiation-inactivation-repopulation model. Based on the available experimental data for the LET dependence of radiobiological parameters and mutation rate, we generalized this formulation to include the effects of radiation quality. We evaluated the secondary cancer risks for protons in the clinical range of LET, i.e., around 4-10 (KeV/μm), which lies in the plateau region of the Bragg peak.For protons, at a fixed radiation dose, we showed that the increase in second cancer risks correlated directly with increasing values of LET to a certain point, and then decreased. Interestingly, we obtained a higher risk for proton LET of 10 KeV/μm compared to the lower LET of 4 KeV/μm in the low dose region. In the case of heavy ions, the risk was higher for Carbon ions than Neon ions (even though they have almost the same LET). We also compared protons and alpha particles with the same LET, and it was interesting to note that the second cancer risks were higher for protons compared to alpha particles in the low-dose region.Overall, this study demonstrated the importance of including LET dependence in the estimation of second cancer risk. Our theoretical risk predictions were noticeably high; however, the biological end points should be tested experimentally for multiple treatment fields and to improve theoretical predictions.

An interesting problem associated with studying the effects of low doses of high atomic number and energy (HZE) particles, as found in space, is that not all cells will necessarily be similarly traversed during exposure, a scenario that greatly complicates the measurement of end points that require time to develop, gene-locus mutation being a perfect example. The standard protocol for measuring mutations at the heterozygous thymidine kinase locus in human lymphoblastoid cells involves waiting three days after treatment for newly induced mutants to fully express, at which time cells are then plated in the presence of the selective agent, and mutants are counted three weeks later. This approach is acceptable as long as all cells are uniformly affected, as is the case with low-linear energy transfer (LET) ionizing radiation. However, for HZE particles some fraction of cells may not be traversed or perhaps would receive fewer than the average number of "hits", and they would continue to grow at or closer to the normal rate, thus outpacing cells that received more damage. As a result, at three days post-treatment, more heavily damaged cells will have been "diluted" by the less damaged ones, and thus the measured mutant frequency (MF) will underestimate actual mutant frequency. We therefore developed a modified approach for measuring mutation that eliminates this problem and demonstrates that the mutagenicity of 1 GeV/n Fe ions are underestimated by a factor of two when using the standard MF protocol. Furthermore, we determined the mutagenic effects of a variety of heavy ions, all of which induced mutations in a linear fashion. We found that the maximal yield of mutations (i.e., highest relative biological efficiency) was about 7.5 times higher at an LET of 70 keV/μ (400 MeV/n Si) than for gamma rays. Nontargeted mutagenicity after treatment with ionizing radiation was also investigated. For each particular ion/energy examined and in agreement with many previous studies, there was no clear evidence of a dose response for bystander mutagenesis, i.e., the MF plateaued. Interestingly, the magnitudes of the bystander MFs induced by different ion/energy combinations did vary, with bystander MFs ranging from 0.8 to 2.2× higher than the background. Furthermore, the nontargeted MFs appeared to reflect a mirror image of that for direct mutagenesis.

Underpinning current models of the mechanisms of the action of radiation is a central role for DNA damage and in particular double-strand breaks (DSBs). For radiations of different LET, there is a need to know the exact yields and distributions of DSBs in human cells. Most measurements of DSB yields within cells now rely on pulsed-field gel electrophoresis as the technique of choice. Previous measurements of DSB yields have suggested that the yields are remarkably similar for different types of radiation with RBE valuesor = 1.0. More recent studies in mammalian cells, however, have suggested that both the yield and the spatial distribution of DSBs are influenced by radiation quality. RBE values for DSBs induced by high-LET radiations are greater than 1.0, and the distributions are nonrandom. Underlying this is the interaction of particle tracks with the higher-order chromosomal structures within cell nuclei. Further studies are needed to relate nonrandom distributions of DSBs to their rejoining kinetics. At the molecular level, we need to determine the involvement of clustering of damaged bases with strand breakage, and the relationship between higher-order clustering over sizes of kilobase pairs and above to localized clustering at the DNA level. Overall, these studies will allow us to elucidate whether the nonrandom distributions of breaks produced by high-LET particle tracks have any consequences for their repair and biological effectiveness.

Continuous depth dose measurements are generally performed in water phantoms. It is now possible to make continuous depth dose measurements in the solid PMMA phantom Plexitom, developed by our group and manufactured by PTW. The mechanical construction of this phantom allows the continuous movement of the ionisation chamber within the solid phantom. The Plexitom is light and very handy. It is very useful for quality assurance, especially to check the radiation quality of the linac.

Ceramic chips of beryllium oxide were exposed to high energy heavy ion beams (He, C, Ne, Ar, and Fe) and the glow curves were analysed. Two comparable peaks at around 203°C and 355°C were found and each peak height showed a different LET dependence. The low temperature peak height (I L ) increased remarkably with LET to about 10 keV.μm -1 and the relative efficiency normalised to that of 137 Cs γ rays took a maximum factor of 1.3. The high temperature peak height (I H ) decreased almost linearly with the logarithm of LET. The ratio of I H to I L decreased exponentially up to 100 keV.μm 1 . These results show a possibility that the glow curve of BeO can be utilised for the evaluation of radiation quality where high LET particles are mixed, as in space.

Radiations of high linear energy transfer (LET) have long been known to have greater biological effectiveness per unit dose than those of low LET, for a wide variety of biological effects. However, values of relative biological effectiveness depend considerably on the biological system and in some instances the values are clearly below unity. The differences between high- and low-LET radiations may be due to many factors, almost all of which are related to radiation track structure in one way or another, and some can in principle lead to qualitative as well as quantitative differences between the radiations. Explanations for LET-dependent differences in effectiveness are discussed over a variety of levels from the multicellular and cellular scale down to the DNA scale, with illustrations from radiobiological data. Information from well-defined slow light ions provide particularly useful analytic data, but practical issues extend also to neutrons and fast heavy ions, which may compound high- and low-LET features. It is suggested that effectiveness of the radiation is determined predominantly by the complex clustered damage that it produces in DNA, but that for high-LET radiations long-term effects are in some instances limited by single-track-survival probabilities of the traversed cells.

This short review summarizes the data obtained with various techniques for measuring the yields of double strand breaks (dsb) produced by particle radiations of differing linear energy transfer (LET) in order to obtain relative biological effectiveness (RBE) values.Studies aimed at understanding the interactions of different types of radiation with cellular DNA have monitored the yields of DNA dsb versus radiation quality. Several techniques have been used to measure dsb yields in mammalian cells, and these include: neutral sedimentation gradients, filter elution and more recently pulsed field gel electrophoresis techniques (PFGE). Recent developments in PFGE have allowed the measurement of both the yields and the distribution of breaks within the genome, which go part of the way to explaining the RBE values close to 1.0 previously measured using other approaches with various radiation qualities. It is clear that future studies to determine the effectiveness of radiations of differing LET must use techniques that determine both yields and distributions of dsb, and assays need to be developed to allow these measurements at biologically relevant doses.

Tritium occurs from both natural and manufactured processes. In the environment, tritium can exist in the form of tritiated water (HTO) and in an organic form known as organically-bound tritium (OBT). Although, the concentrations of environmental OBT are relatively low, there is concern that current risk factors may underestimate the risk from OBT. Because tritium poses an internal hazard at cellular levels, microdosimetric techniques provide suitable tools for the study of radiation quality of tritium. In this study, microdosimetric simulations are performed for tritium uniformly distributed in a medium, and for tritium bound to biologically critical sites of dimensions from 10 nm to 2 microm. Results of local energy density are different for these two cases in microscopic regions. Based on the spatial distribution of energy deposition, dose mean lineal energies are calculated for tritium in forms of HTO and OBT. The dose mean lineal energies of OBT are about a factor of 1.7 higher than those of HTO in a wide range of target dimensions of biological interest. The results are consistent with radiobiological findings that OBT is about twice as effective as that of HTO.

The commonly used parameters of radiation quality, LET and linear energy, exhibit their shortcomings when ranges of charged particles are comparable with dimensions of subcellular structures. An interpretation of this fact is given and a new parameter, the linear energy deposit, is introduced. On this basis a simple model for estimation of RBE of electron-photon fields has been developed and applied to monoenergetic photon sources in the energy range of 10 2 -10 6 eV.

The amount of chromosomal damage induced in synchronous V79 cells by either 250 kV X-rays or 4.6 MeV/u Ar ions (LET: 1850 keV/microns) was determined at five successive sampling times. The experiments show that the time course of the appearance of damaged cells is strongly influenced by radiation-induced cell cycle perturbations and mitotic delay and depends on radiation quality and dose. The yield of chromosomal damage was found to increase with sampling time, but this increase was more pronounced for Ar ions. Because of the observed differences in the yield time profiles induced by sparsely and densely ionizing radiation the contribution of each sample to the overall damage was considered, i.e. the total (time integrated) amount of damage was determined. The obtained data are interpreted in terms of differences in the spatial energy deposition by sparsely and densely ionizing radiation.

Microdosimetric spectra were measured in order to gain the microdosimetric parameters of some epithermal neutron fields. Changes in dose mean lineal energy y D as a function of depth of heavy water showed a trend of softening with heavy water of the beam. The neutron absorbed dose was obtained by using the frequency mean lineal energy. Results show good agreement with measurements with the activation method using gold foil. This study demonstrated how microdosimetric parameters change in radiation quality as a function of heavy water depth.