Radiosensitivity and transgenerational effects in non-human species.

The ALLIANCE working group on effects of ionising radiation on wildlife brings together European researchers to work on the topics of radiosensitivity and transgenerational effects in non-human biota. Differences in radiation sensitivity across species and phyla are poorly understood, but have important implications for understanding the overall effects of radiation and for radiation protection; for example, sensitive species may require special attention in monitoring and radiation protection, and differences in sensitivity between species also lead to overall effects at higher levels (community, ecosystem), since interactions between species can be altered. Hence, understanding the mechanisms of interspecies radiation sensitivity differences may help to clarify mechanisms underpinning intraspecies variation. Differences in sensitivity may only be revealed when organisms are exposed to ionising radiation over several generations. This issue of potential long-term or hereditary effects for both humans and wildlife exposed to low doses of ionising radiation is a major concern. Animal and plant studies suggest that gamma irradiation can lead to observable effects in the F1 generation that are not attributable to inheritance of a rare stable DNA mutation. Several studies have provided evidence of an increase in genomic instability detected in germ or somatic cells of F1 organisms from exposed F0 organisms. This can lead to induced radiosensitivity, and can result in phenotypic effects or lead to reproductive effects and teratogenesis. In particular, studies have been conducted to understand the possible role of epigenetic modifications, such as DNA methylation, histone modifications, or expression of non-coding RNAs in radiosensitivity, as well as in adaptation effects. As such, research using biological models in which the relative contribution of genetic and epigenetic processes can be elucidated is highly valuable.

Detection of locally radio-recurrent prostate cancer at multiparametric MRI: Can dynamic contrast-enhanced imaging be omitted?

OBJECTIVE: The goal of this study was to assess the added value of dynamic contrast-enhanced (DCE) imaging in detecting locally radio-recurrent prostate cancer using multiparametric magnetic resonance imaging (mpMRI) at 3Tesla (T). MATERIALS AND METHODS: We retrospectively analyzed 45 patients with rising prostate-specific antigen level after prostate radiotherapy who underwent mpMRI [T2-weighted (T2w), diffusion-weighted (Dw) and DCE imaging] at 3T before prostate biopsy. Four readers assigned a 5-level Likert score of cancer likelihood in 8 prostate sectors (6 sextants, 2 seminal vesicles) on T2w+Dw and T2w+Dw+DCE images. Biopsy results were used as the standard of reference. RESULTS: T2w+Dw and T2w+Dw+DCE imaging had similar areas under the receiver operating characteristic curves on per-sector (0.87-0.89 vs. 0.87-0.89; P=0.19-0.78) and per-lobe (0.82-0.94 vs. 0.80-0.91; P=0.21-0.84) analysis. Using a Likert score≥2/5 for diagnosis threshold, T2w+Dw+DCE imaging showed non-significantly higher sensitivities on per-sector (0.56-0.72 vs. 0.52-0.73, P=0.34-0.69) and per-lobe (0.80-0.90 vs. 0.73-0.88; P=0.63-0.99) analysis. It also showed non-significantly lower specificities on per-sector (0.74-0.89 vs. 0.82-0.89; P=0.09-0.99) and per-lobe (0.48-0.81 vs. 0.61-0.84; P=0.10-0.99) analysis. Weighted kappa values were respectively 0.57-0.70 and 0.55-0.66 for T2w+Dw and T2w+Dw+DCE imaging at the sector level, and 0.66-0.83 and 0.58-0.85 at the lobe level. CONCLUSION: The use of DCE MR imaging tends to increase sensitivity and decrease specificity for all readers, but the differences are not significant.

Establishing relationships between environmental exposures to radionuclides and the consequences for wildlife: inferences and weight of evidence.

Ecological risk assessments for radioactive substances are based on a number of inference rules to compensate for knowledge gaps, and generally require the implementation of a weight-of-evidence approach. Until recently, dose (rate)-response relationships used to derive radioprotection criteria for wildlife have mainly relied on laboratory studies from a limited number of species as representatives of biodiversity. There is no doubt that additional knowledge, combined with advanced conceptual and mathematical approaches, is needed to develop general rules and increase confidence when extrapolating from test species to complex biological/ecological systems. Moreover, field data sets based on robust sampling strategies are still needed to validate benchmark values derived from controlled laboratory tests, and to indicate potential indirect ecological effects, if any. This paper illustrates, through several examples, the need for implementing a combined laboratory-field-model approach to obtain science-based benchmark doses (or dose rates) (e.g. screening benchmarks for ecological risk assessments or derived consideration reference levels), based on robust meta-analysis of dose-effect relationships covering ecologically relevant exposure time scales, species, and endpoints.

An invitation to contribute to a strategic research agenda in radioecology.

With intentions of integrating a portion of their respective research efforts into a trans-national programme that will enhance radioecology, eight European organisations recently formed the European Radioecology ALLIANCE (www.er-alliance.org). The ALLIANCE is an Association open to other organisations throughout the world with similar interests in promoting radioecology. The ALLIANCE members recognised that their shared radioecological research could be enhanced by efficiently pooling resources among its partner organizations and prioritising group efforts along common themes of mutual interest. A major step in this prioritisation process was to develop a Strategic Research Agenda (SRA). An EC-funded Network of Excellence in Radioecology, called STAR (Strategy for Allied Radioecology), was formed, in part, to develop the SRA. This document is the first published draft of the SRA. The SRA outlines a suggested prioritisation of research topics in radioecology, with the goal of improving research efficiency and more rapidly advancing the science. It responds to the question: "What topics, if critically addressed over the next 20 years, would significantly advance radioecology?" The three Scientific Challenges presented within the SRA, with their 15 associated research lines, are a strategic vision of what radioecology can achieve in the future. Meeting these challenges will require a directed effort and collaboration with many organisations the world over. Addressing these challenges is important to the advancement of radioecology and in providing scientific knowledge to decision makers. Although the development of the draft SRA has largely been a European effort, the hope is that it will initiate an open dialogue within the international radioecology community and its stakeholders. This is an abbreviated document with the intention of introducing the SRA and inviting contributions from interested stakeholders. Critique and input for improving the SRA are welcomed via a link on the STAR website (www.star-radioecology.org).

Issues and practices in the use of effects data from FREDERICA in the ERICA Integrated Approach.

The ERICA Integrated Approach requires that a risk assessment screening dose rate is defined for the risk characterisation within Tiers 1 and 2. At Tier 3, no numerical screening dose rate is used, and the risk characterisation is driven by methods that can evaluate the possible effects of ionising radiation on reproduction, mortality and morbidity. Species sensitivity distribution has been used to derive the ERICA risk assessment predicted no-effect dose rate (PNEDR). The method used was based on the mathematical processing of data from FRED (FASSET radiation effects database merged with the EPIC database to form FREDERICA) and resulted in a PNEDR of 10 microGy/h. This rate was assumed to ascribe sufficient protection of all ecosystems from detrimental effects on structure and function under chronic exposure. The value was weighed against a number of points of comparison: (i) PNEDR values obtained by application of the safety factor method, (ii) background levels, (iii) dose rates triggering effects on radioactively contaminated sites and (iv) former guidelines from literature reviews. In Tier 3, the effects analysis must be driven by the problem formulation and is thus highly case specific. Instead of specific recommendations on numeric values, guidance on the sorts of methods that may be applied for refined effect analysis is provided and illustrated.

Modelling the propagation of effects of chronic exposure to ionising radiation from individuals to populations.

This study evaluated the potential effect of ionising radiation on population growth using simple population models and parameter values derived from chronic exposure experiments in two invertebrate species with contrasting life-history strategies. In the earthworm Eisenia fetida, models predicted increasing delay in population growth with increasing gamma dose rate (up to 0.6 generation times at 11 mGy h(-1)). Population extinction was predicted at 43 mGy h(-1). In the microcrustacean Daphnia magna, models predicted increasing delay in population growth with increasing alpha dose rate (up to 0.8 generation times at 15.0 mGy h(-1)), only after two successive generations were exposed. The study examined population effects of changes in different individual endpoints (including survival, number of offspring produced and time to first reproduction). Models showed that the two species did not respond equally to equivalent levels of change, the fast growing daphnids being more susceptible to reduction in fecundity or delay in reproduction than the slow growing earthworms. This suggested that susceptibility of a population to ionising radiation cannot be considered independent of the species' life history.

Increased effects of internal alpha irradiation in Daphnia magna after chronic exposure over three successive generations.

A 70-day experiment was performed with Daphnia magna exposed to waterborne Am-241 on a range of concentrations (from 0.4 to 40 Bq ml(-1)) in order to test chronic effects of internal alpha irradiation on respiration, somatic growth and reproduction over three successive generations. Changes in Am-241 concentrations were followed in the water and in daphnid tissues, eggs and cuticles. Corresponding average dose rates of 0.3, 1.5 and 15 mGy h(-1) were estimated. This study confirmed that oxygen consumption increased significantly in the first generation (F0) after 6 days of exposure to a dose rate >or=1.5 mGy h(-1). Consequences were limited to a reduction in body length (5%) and dry mass of females (16%) and eggs (8%) after 23 days of exposure, while mortality and fecundity remained unaffected. New cohorts were started with neonates of broods 1 and 5, to examine potential consequences of the reduced mass of offspring for subsequent exposed generations. Results strongly contrasted with those observed in F0. At the highest dose rate, an early mortality of 38-90% affected juveniles while survivors showed delayed reproduction and reduced fecundity in F1 and F2. At 0.3 and 1.5 mGy h(-1), mortality ranged from 31 to 38% of daphnids depending on dose rate, but was observed only in generation F1 started with neonates of the brood 1. Reproduction was affected through a reduction in the proportion of breeding females, occurring in the first offspring generation at 1.5 mGy h(-1) (to 62% of total daphnids) and in the second generation at 0.3 mGy h(-1) (to 69% of total daphnids). Oxygen consumption remained significantly higher at dose rates >or=0.3 mGy h(-1) than in the control in almost every generation. Body size and mass continued decreasing in relation to dose rate, with a significant reduction in mass ranging from 15% at 0.3 mGy h(-1) to 27% at 15 mGy h(-1) in the second offspring generation.

Effects of chronic internal alpha irradiation on physiology, growth and reproductive success of Daphnia magna.

Daphnids were chronically exposed to waterborne Am-241, an alpha-emitting radionuclide, ranging in concentration from 0.4 to 40 Bq ml(-1). Am-241 amounts were monitored in the medium, daphnid tissues and cuticles. Corresponding average dose rates of 0.02, 0.11 and 0.99 mGy h(-1) were calculated for whole organisms with internal alpha-radiation contributing 99% of total dose rates. Effects of internal alpha irradiation on respiration and ingestion rates, adult, egg and neonate individual dry masses, fecundity and larval resistance to starvation were examined in 23-day experiments. Daphnids showed increased respiratory demand after 23 days at the highest dose rate, suggesting increased metabolic cost of maintenance due to coping with alpha radiological stress. Although no effect was detected on ingestion rates between contaminated and control daphnids, exposure to dose rates of 0.11 mGy h(-1) or higher, resulted in a significant 15% reduction in body mass. Fecundity remained unchanged over the 23-day period, but individual masses of eggs and neonates were significantly smaller compared to the control. This suggested that increased metabolic expenditure in chronically alpha-radiated daphnids came at the expense of their energy investment per offspring. As a consequence, neonates showed significantly reduced resistance to starvation at every dose rate compared to the control. Our observations are discussed in comparison with literature results reported for cadmium, a chemical toxicant which affects feeding activity and strongly reduces individual energy uptake.

Two currents activated by epidermal growth factor in EGFR-T17 fibroblasts.

Application of 10 nM Epidermal Growth Factor (EGF) to single EGFR-T17 fibroblasts induced a marked hyperpolarization that could last for tens of minutes; in many cases the first transient was followed by a series of oscillations of the membrane potential. The outward current responsible for the hyperpolarizing response could be recorded simultaneously to an increase in the intracellular calcium concentration, as measured with the fluorescent indicator fura-2. The conductance was nearly linear in the voltage range from -100 to +50 mV. While the EGF-induced current had many characteristics of a K+ current and was strongly reduced by 50 nM charybdotoxin (ChTx), its reversal potential was apparently more negative than the potassium equilibrium potential (VK). The application of 2 microM ouabain prior to EGF stimulation produced responses that were similar to those obtained without ouabain; however, under these conditions the EGF-induced current showed a reversal potential of -96.6 +/- 3.2 mV, very close to VK. Simultaneous application of both 2 microM ouabain and 50 nM ChTx completely abolished the response. It can be concluded that the response to EGF stimulation in EGFR-T17 cells consists of two components: the first is a current carried through Ca(2+)-activated K+ channels; the second is due to the acceleration of the operation of the Na+/K(+)-ATPase.