Preliminary FISH-based assessment of external dose for residents exposed on the Techa River

This paper presents the results of a feasibility cytogenetic study using the fluorescence in situ hybridization (FISH) translocation assay for residents of villages located on the Techa River (Southern Urals, Russia) contaminated with liquid radioactive wastes from the Mayak plutonium facility in 1949-1956. The study was conducted with two groups of donors that differed in their main pathways of exposure. The first group comprised 18 residents of the middle Techa region who were exposed predominantly from ingestion of radionuclides (mostly (89,90)Sr) via the river water and local foodstuffs. The second group included 20 residents of Metlino, the closest village to the site of releases, who were exposed to external γ radiation from the contaminated river bank and exposed internally from dietary intake of radionuclides. A significant linear dependence between the radiation-induced translocation frequency and individual red bone marrow dose from incorporated (89,90)Sr, calculated with the Techa River Dosimetry System (TRDS), was found in the first group of donors. This allowed us to take the contribution of (89,90)Sr to the total radiation-induced translocation frequency into account for the second group of donors and to analyze translocations resulting from external γ-ray exposure. Individual doses from external exposure derived from the corrected translocation frequency for the second group of donors (Metlino residents), using a linear dose-response coefficient of 0.015 translocation/cell/Gy recommended by Edwards et al. in 2005, were shown to vary up to 2.1 Gy, with an average value of 0.48 Gy, which was in agreement with TRDS-based external dose estimates for Metlino residents.     

Evidence for significant heritability of apoptotic and cell cycle responses to ionising radiation

Genetic factors are likely to affect individual cancer risk, but few quantitative estimates of heritability are available. Public health radiation protection policies do not in general take this potentially important source of variation in risk into account. Two surrogate cellular assays that relate to cancer susceptibility have been developed to gain an insight into the role of genetics in determining individual variation in radiosensitivity. These flow cytometric assays for apoptosis induction and cell cycle delay following radiation are sufficiently sensitive to distinguish lymphocytes from a healthy donor population from those of a sample of obligate carriers of ATM mutations (P = 0.01 and P = 0.02, respectively). Analysis of 54 unselected twin pairs (38 dizygotic, 16 monozygotic) indicated much greater intrapair correlation in response in monozygotic than in dizygotic pairs. Structural equation modelling indicated that models including unique environmental factors only fitted the data less well than those incorporating two or more of additive genetic factors, common environmental factors and unique environmental factors. A model incorporating additive genetic factors and unique environmental factors yielded estimates of heritability for the two traits of 68% (95% CI 40–82%, cell cycle) and 59% (95% CI 22–79%, apoptosis). Thus, these data suggest that genetic factors contribute significantly to human variation in these two measures of radiosensitivity that relate to cancer susceptibility.     

Web-based scoring of the dicentric assay,a collaborative biodosimetric scoring strategy for population triage in large scale radiation accidents

In the case of a large scale radiation accident high throughput methods of biological dosimetry for population triage are needed to identify individuals requiring clinical treatment. The dicentric assay performed in web-based scoring mode may be a very suitable technique. Within the MULTIBIODOSE EU FP7 project a network is being established of 8 laboratories with expertise in dose estimations based on the dicentric assay. Here, the manual dicentric assay was tested in a web-based scoring mode. More than 23,000 high resolution images of metaphase spreads (only first mitosis) were captured by four laboratories and established as image galleries on the internet (cloud). The galleries included images of a complete dose effect curve (0–5.0 Gy) and three types of irradiation scenarios simulating acute whole body, partial body and protracted exposure. The blood samples had been irradiated in vitro with gamma rays at the University of Ghent, Belgium. Two laboratories provided image galleries from Fluorescence plus Giemsa stained slides (3 h colcemid) and the image galleries from the other two laboratories contained images from Giemsa stained preparations (24 h colcemid). Each of the 8 participating laboratories analysed 3 dose points of the dose effect curve (scoring 100 cells for each point) and 3 unknown dose points (50 cells) for each of the 3 simulated irradiation scenarios. At first all analyses were performed in a QuickScan Mode without scoring individual chromosomes, followed by conventional scoring (only complete cells, 46 centromeres). The calibration curves obtained using these two scoring methods were very similar, with no significant difference in the linear-quadratic curve coefficients. Analysis of variance showed a significant effect of dose on the yield of dicentrics, but no significant effect of the laboratories, different methods of slide preparation or different incubation times used for colcemid. The results obtained to date within the MULTIBIODOSE project by a network of 8 collaborating laboratories throughout Europe are very promising. The dicentric assay in the web based scoring mode as a high throughput scoring strategy is a useful application for biodosimetry in the case of a large scale radiation accident.     

Eurados review of retrospective dosimetry techniques for internal exposures to ionising radiation and their applications

Radiation and Environmental Biophysics - This work presents an overview of the applications of retrospective dosimetry techniques in case of incorporation of radionuclides. The fact that internal...     

Nonlinear ionizing radiation-induced changes in eye lens cell proliferation,cyclin D1 expression and lens shape

Elevated cataract risk after radiation exposure was established soon after the discovery of X-rays in 1895. Today, increased cataract incidence among medical imaging practitioners and after nuclear incidents has highlighted how little is still understood about the biological responses of the lens to low-dose ionizing radiation (IR). Here, we show for the first time that in mice, lens epithelial cells (LECs) in the peripheral region repair DNA double strand breaks (DSB) after exposure to 20 and 100 mGy more slowly compared with circulating blood lymphocytes, as demonstrated by counts of γH2AX foci in cell nuclei. LECs in the central region repaired DSBs faster than either LECs in the lens periphery or lymphocytes. Although DSB markers (γH2AX, 53BP1 and RAD51) in both lens regions showed linear dose responses at the 1 h timepoint, nonlinear responses were observed in lenses for EdU (5-ethynyl-2′-deoxy-uridine) incorporation, cyclin D1 staining and cell density after 24 h at 100 and 250 mGy. After 10 months, the lens aspect ratio was also altered, an indicator of the consequences of the altered cell proliferation and cell density changes. A best-fit model demonstrated a dose-response peak at 500 mGy. These data identify specific nonlinear biological responses to low (less than 1000 mGy) dose IR-induced DNA damage in the lens epithelium.