| 1. |
- Daşu, Alexandru, et al.
(författare)
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Inducible repair and intrinsic radiosensitivity: a complex but predictable relationship?
- 2000
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 153:3, s. 279-288
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Tidskriftsartikel (refereegranskat)abstract
- Two groups have proposed a simple linear relationship between inducible radioresistance in a variety of mammalian cells and their intrinsic radiosensitivity at 2 Gy (Lambin et al., Int.J. Radiat. Biol. 69, 279-290, 1996; Alsbeih and Raaphorst, unpublished results, 1997). The inducible repair response (IRR) is quantified as a ratio, alpha(S)/alpha(R), i.e. the slope in the hypersensitive low-dose region, alpha(S), relative to the alpha(R) term of the classical linear-quadratic formula. These proposals imply that the intrinsic radiosensitivity at clinically relevant doses is directly linked to the cell's ability to mount an adaptive response as a result of exposure to very low doses of radiation. We have re-examined this correlation and found that the more extensive data set now available in the literature does not support the contention of a simple linear relationship. The two parameters are correlated, but by a much more complex relationship. A more logical fit is obtained with a log-linear equation. A series of log-linear curves are needed to describe the correlation between IRR and SF2, because of the spectrum of alpha/beta ratios among the cell lines and hence the confounding effect of the beta term at a dose of 2 Gy. The degree of repair competence before irradiation starts could also be a major factor in the apparent magnitude of the amount of repair induced. There appears to be a systematic difference in the data sets from different series of cell lines that have been obtained using flow cytometry techniques in the laboratory in Vancouver and using dynamic microscope imaging at the Gray Laboratory. We suggest that the use of a brief exposure to a laser beam in flow cytometry before the cells are irradiated might itself partially induce a stress response and change the DNA repair capacity of the cells. The clinical consequences of the relationship for predicting the benefits of altered fractionation schedules are discussed. [ru5]
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| 2. |
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| 3. |
- Naumburg, Estelle, et al.
(författare)
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Intrauterine exposure to diagnostic X rays and risk of childhood leukemia subtypes
- 2001
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 156, s. 718-
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between childhood leukemia and prenatal exposure to low-dose ionizing radiation remains debatable. This population-based case-control study investigated the association between prenatal exposure to diagnostic X-ray examinations (for different types of examinations and at different stages of pregnancy) and the risk of childhood lymphatic and myeloid leukemia. All children born and diagnosed with leukemia between 1973-1989 in Sweden (578 lymphatic and 74 myeloid) were selected as cases, and each was matched (by sex and year of birth) to a healthy control child (excluding Down's syndrome). Exposure data were abstracted blindly from all available medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression. It was found that prenatal X-ray examinations resulting in direct fetal exposure were not associated with a significant overall increased risk for childhood leukemia (OR = 1.11, 95% CI 0.83-1.47), for lymphatic leukemia (OR = 1.04, 95% CI 0.77-1.40), or for myeloid leukemia (OR = 1.49, 95% CI 0.48-4.72). There was little evidence of a dose response or variation in risk by trimester of exposure or age at diagnosis. Thus X-ray examinations performed during pregnancy in the 1970s and 1980s in Sweden did not affect the risk of childhood leukemia discernibly.
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| 4. |
- Olsson, Sara, 1970-, et al.
(författare)
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EPR Dosimetric Properties of 2-Methylalanine : EPR, ENDOR and FT-EPR Investigations
- 2002
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 157:2, s. 113-121
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Tidskriftsartikel (refereegranskat)abstract
- To find an EPR dosimeter material that is sensitive enough for clinical use, the substance 2-methylalanine (2MA) with the chemical structure (CH3)2C(NH3+)COO− was tested for its sensitivity to ionizing radiation, dose response, and radical stability over time. At equal and moderate settings of microwave power and modulation amplitude, 2MA was found to be 70% more sensitive than l-α-alanine, which is the most common EPR dosimeter material today. The dose response is linear, at least in the dose range of interest (0.5–100 Gy), and the time-dependent variations in signal intensity are very small and may be corrected for easily. The energy dependence of the stopping power and energy absorption was calculated and was found to be similar to that of alanine. The dependence of the signal intensity on microwave power and modulation amplitude was investigated, and the optimal settings were found to be 25 mW (Bruker ER 4102ST) and 12 gauss, respectively. Single crystals of 2MA were analyzed using ENDOR and ENDOR-induced EPR to identify the radiation-induced radicals that formed. Only one radical, in which the amino group is detached from the original molecule, was identified. This radical is obviously dominating and is apparently the only one relevant for dosimetry purposes. The complete set of coupling parameters for three hyperfine couplings is reported. The power saturation properties and spectral line width are ruled by the relaxation times T1 and T2. To determine the relaxation times of 2MA, pulsed EPR experiments were performed on single crystals. Two different values of T1 were obtained, one in the range 1–3 µs, shown to be of importance for the dosimetry properties, and another that is strongly anisotropic with a value between 10 and 35 µs that does not seem to affect the saturation behavior. T2 was estimated to be of the order of 200–300 ns.
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| 5. |
- Abend, M., et al.
(författare)
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RENEB Inter-Laboratory Comparison 2021 : The Gene Expression Assay
- 2023
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 199:6, s. 598-615
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Tidskriftsartikel (refereegranskat)abstract
- Early and high-throughput individual dose estimates are essential following large-scale radiation exposure events. In the context of the Running the European Network for Biodosimetry and Physical Dosimetry (RENEB) 2021 exercise, gene expression assays were conducted and their corresponding performance for dose-assessment is presented in this publication. Three blinded, coded whole blood samples from healthy donors were exposed to 0, 1.2 and 3.5 Gy X-ray doses (240 kVp, 1 Gy/min) using the X-ray source Yxlon. These exposures correspond to clinically relevant groups of unexposed, low dose (no severe acute health effects expected) and high dose exposed individuals (requiring early intensive medical health care). Samples were sent to eight teams for dose estimation and identification of clinically relevant groups. For quantitative reverse transcription polymerase chain reaction (qRT-PCR) and microarray analyses, samples were lysed, stored at 20°C and shipped on wet ice. RNA isolations and assays were run in each laboratory according to locally established protocols. The time-to-result for both rough early and more precise later reports has been documented where possible. Accuracy of dose estimates was calculated as the difference between estimated and reference doses for all doses (summed absolute difference, SAD) and by determining the number of correctly reported dose estimates that were defined as ±0.5 Gy for reference doses <2.5 Gy and ±1.0 Gy for reference doses >3 Gy, as recommended for triage dosimetry. We also examined the allocation of dose estimates to clinically/diagnostically relevant exposure groups. Altogether, 105 dose estimates were reported by the eight teams, and the earliest report times on dose categories and estimates were 5 h and 9 h, respectively. The coefficient of variation for 85% of all 436 qRT-PCR measurements did not exceed 10%. One team reported dose estimates that systematically deviated several-fold from reported dose estimates, and these outliers were excluded from further analysis. Teams employing a combination of several genes generated about two-times lower median SADs (0.8 Gy) compared to dose estimates based on single genes only (1.7 Gy). When considering the uncertainty intervals for triage dosimetry, dose estimates of all teams together were correctly reported in 100% of the 0 Gy, 50% of the 1.2 Gy and 50% of the 3.5 Gy exposed samples. The order of dose estimates (from lowest to highest) corresponding to three dose categories (unexposed, low dose and highest exposure) were correctly reported by all teams and all chosen genes or gene combinations. Furthermore, if teams reported no exposure or an exposure >3.5 Gy, it was always correctly allocated to the unexposed and the highly exposed group, while low exposed (1.2 Gy) samples sometimes could not be discriminated from highly (3.5 Gy) exposed samples. All teams used FDXR and 78.1% of correct dose estimates used FDXR as one of the predictors. Still, the accuracy of reported dose estimates based on FDXR differed considerably among teams with one team's SAD (0.5 Gy) being comparable to the dose accuracy employing a combination of genes. Using the workflow of this reference team, we performed additional experiments after the exercise on residual RNA and cDNA sent by six teams to the reference team. All samples were processed similarly with the intention to improve the accuracy of dose estimates when employing the same workflow. Re-evaluated dose estimates improved for half of the samples and worsened for the others. In conclusion, this inter-laboratory comparison exercise enabled (1) identification of technical problems and corrections in preparations for future events, (2) confirmed the early and high-throughput capabilities of gene expression, (3) emphasized different biodosimetry approaches using either only FDXR or a gene combination, (4) indicated some improvements in dose estimation with FDXR when employing a similar methodology, which requires further research for the final conclusion and (5) underlined the applicability of gene expression for identification of unexposed and highly exposed samples, supporting medical management in radiological or nuclear scenarios.
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| 6. |
- Abramenkovs, Andris, et al.
(författare)
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Measurement of DNA-Dependent Protein Kinase Phosphorylation Using Flow Cytometry Provides a Reliable Estimate of DNA Repair Capacity
- 2017
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Ingår i: Radiation Research. - : RADIATION RESEARCH SOC. - 0033-7587 .- 1938-5404. ; 188:6, s. 597-604
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Tidskriftsartikel (refereegranskat)abstract
- Uncontrolled generation of DNA double-strand breaks (DSBs) in cells is regarded as a highly toxic event that threatens cell survival. Radiation-induced DNA DSBs are commonly measured by pulsed-field gel electrophoresis, microscopic evaluation of accumulating DNA damage response proteins (e.g., 53BP1 or gamma-H2AX) or flow cytometric analysis of gamma-H2AX. The advantage of flow cytometric analysis is that DSB formation and repair can be studied in relationship to cell cycle phase or expression of other proteins. However, gamma-H2AX is not able to monitor repair kinetics within the first 60 min postirradiation, a period when most DSBs undergo repair. A key protein in non-homologous end joining repair is the catalytic subunit of DNA-dependent protein kinase. Among several phosphorylation sites of DNA-dependent protein kinase, the threonine at position 2609 (T2609), which is phosphorylated by ataxia telangiectasia mutated (ATM) or DNA-dependent protein kinase catalytic subunit itself, activates the end processing of DSB. Using flow cytometry, we show here that phosphorylation at T2609 is faster in response to DSBs than gamma-H2AX. Furthermore, flow cytometric analysis of T2609 resulted in a better representation of fast repair kinetics than analysis of gamma-H2AX. In cells with reduced ligase IV activity, and wild-type cells where DNA-dependent protein kinase activity was inhibited, the reduced DSB repair capacity was observed by T2609 evaluation using flow cytometry. In conclusion, flow cytometric evaluation of DNA-dependent protein kinase T2609 can be used as a marker for early DSB repair and gives a better representation of early repair events than analysis of gamma-H2AX.
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| 7. |
- Bajinskis, Ainars, et al.
(författare)
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Low-Dose/Dose-Rate gamma Radiation Depresses Neural Differentiation and Alters Protein Expression Profiles in Neuroblastoma SH-SY5Y Cells and C17.2 Neural Stem Cells
- 2011
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 175:2, s. 185-192
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Tidskriftsartikel (refereegranskat)abstract
- The effects of low doses of ionizing radiation on cellular development in the nervous system are presently unclear. The focus of the present study was to examine low-dose gamma-radiation-induced effects on the differentiation of neuronal cells and on the development of neural stem cells to glial cells. Human neuroblastoma SH-SY5Y cells were exposed to (137)Cs gamma rays at different stages of retinoic acid-induced neuronal differentiation, and neurite formation was determined 6 days after exposure. When SH-SY5Y cells were exposed to low-dose-rate gamma rays at the onset of differentiation, the number of neurites formed per cell was significantly less after exposure to either 10, 30 or 100 mGy compared to control cells. Exposure to 10 and 30 mGy attenuated differentiation of immature C17.2 mouse-derived neural stem cells to glial cells, as verified by the diminished expression of glial fibrillary acidic protein. Proteomic analysis of the neuroblastoma cells by 2D-PAGE after 30 mGy irradiation showed that proteins involved in neuronal development were downregulated. Proteins involved in cell cycle and proliferation were altered in both cell lines after exposure to 30 mGy; however, the rate of cell proliferation was not affected in the low-dose range. The radiation-induced attenuation of differentiation and the persistent changes in protein expression is indicative of an epigenetic rather than a cytotoxic mechanism. (C) 2011 by Radiation Research Society
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| 8. |
- Barquinero, J-F., et al.
(författare)
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RENEB Inter-Laboratory Comparison 2021 : The FISH-Based Translocation Assay
- 2023
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 199:6, s. 583-590
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Tidskriftsartikel (refereegranskat)abstract
- Translocation analysis using fluorescence in situ hybridization (FISH) is the method of choice for dose assessment in case of chronic or past exposures to ionizing radiation. Although it is a widespread technique, unlike dicentrics, the number of FISH-based inter-laboratory comparisons is small. For this reason, although the current Running the European Network of Biological and Physical retrospective Dosimetry (RENEB) inter-laboratory comparison 2021 was designed as a fast response to a real emergency scenario, it was considered a good opportunity to perform an inter-laboratory comparison using the FISH technique to gain further experience. The Bundeswehr Institute of Radiobiology provided peripheral blood samples from one healthy human volunteer. Three test samples were irradiated with blinded doses of 0, 1.2, and 3.5 Gy, respectively. Samples were then sent to the seven participating laboratories. The FISH technique was applied according to the standard procedure of each laboratory. Both, the frequency of translocations and the estimated dose for each sample were sent to the coordinator using a special scoring sheet for FISH. All participants sent their results in due time. However, although it was initially requested to send the results based on the full analysis, evaluating 500 equivalent cells, most laboratories only sent the results based on triage, with a smaller number of analyzed cells. In the triage analysis, there was great heterogeneity in the number of equivalent cells scored. On the contrary, for the full analysis, this number was more homogeneous. For all three samples, one laboratory showed outlier yields compared to the other laboratories. Excluding these results, in the triage analysis, the frequency of translocations in sample no. 1 ranged from 0 to 0.013 translocations per cell, and for samples no. 2 and no. 3 the genomic mean frequency were 0.27 +/- 0.03 and 1.47 +/- 0.14, with a coefficient of variation of 0.29 and 0.23 respectively. Considering only results obtained in the triage analysis for sample no. 1, all laboratories, except one, classified this sample as the non-irradiated one. For sample no. 2, excluding the outlier value, the mean reported dose was 1.74 +/- 0.16 Gy indicating a mean deviation of about 0.5 Gy to the delivered dose of 1.2 Gy. For sample no. 3 the mean dose estimated was 4.21 +/- 0.21 Gy indicating a mean deviation of about 0.7 Gy to the delivered dose of 3.5 Gy. In the frame of RENEB, this is the second FISH-based inter-laboratory comparison. The whole exercise was planned as a response to an emergency, therefore, a triage analysis was requested for all the biomarkers except for FISH. Although a full analysis was initially requested for FISH, most of the laboratories reported only a triage-based result. The main reason is that it was not clearly stated what was required before starting the exercise. Results show that most of the laboratories successfully discriminated unexposed and irradiated samples from each other without any overlap. A good agreement in the observed frequencies of translocations was observed but there was a tendency to overestimate the delivered doses. Efforts to improve the harmonization of this technique and subsequent exercises to elucidate the reason for this trend should be promoted.
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| 9. |
- Berger, Thomas, et al.
(författare)
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The MATROSHKA Experiment: Results and Comparison from Extravehicular Activity (MTR-1) and Intravehicular Activity (MTR-2A/2B) Exposure
- 2013
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Ingår i: Radiation Research. - 1938-5404 .- 0033-7587. ; 180:6, s. 622-637
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Tidskriftsartikel (refereegranskat)abstract
- Astronauts working and living in space are exposed to considerably higher doses and different qualities of ionizing radiation than people on Earth. The multilateral MATROSHKA (MTR) experiment, coordinated by the German Aerospace Center, represents the most comprehensive effort to date in radiation protection dosimetry in space using an anthropomorphic upper-torso phantom used for radiotherapy treatment planning. The anthropomorphic upper-torso phantom maps the radiation distribution as a simulated human body installed outside (MTR-1) and inside different compartments (MTR-2A: Pirs; MTR-2B: Zvezda) of the Russian Segment of the International Space Station. Thermoluminescence dosimeters arranged in a 2.54 cm orthogonal grid, at the site of vital organs and on the surface of the phantom allow for visualization of the absorbed dose distribution with superior spatial resolution. These results should help improve the estimation of radiation risks for long-term human space exploration and support benchmarking of radiation transport codes.
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| 10. |
- Brehwens, Karl, et al.
(författare)
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Cytogenetic damage in cells exposed to ionizing radiation under conditions of a changing dose rate
- 2010
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 173:3, s. 283-9
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Tidskriftsartikel (refereegranskat)abstract
- The current international paradigm on the biological effects of radiation is based mainly on the effects of dose with some consideration for the dose rate. No allowance has been made for the potential influence of a changing dose rate (second derivative of dose), and the biological effects of exposing cells to changing dose rates have never been analyzed. This paper provides evidence that radiation effects in cells may depend on temporal changes in the dose rate. In these experiments, cells were moved toward or away from an X-ray source. The speed of movement, the time of irradiation, and the temperature during exposure were controlled. Here we report the results of the first experiments with TK6 cells that were exposed at a constant dose rate, at an increasing dose rate, or at a decreasing dose rate. The average dose rate and the total dose were same for all samples. Micronuclei were scored as the end point. The results show that the level of cytogenetic damage was higher in cells exposed to a decreasing dose rate compared to both an increasing and a constant dose rate. This finding may suggest that the second derivative of dose may influence radiation risk estimates, and the results should trigger further studies on this issue.
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| 11. |
- Claesson, Kristina, 1965, et al.
(författare)
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Relative biological effectiveness of the alpha-particle emitter (211)At for double-strand break induction in human fibroblasts.
- 2007
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Ingår i: Radiation research. - 0033-7587 .- 1938-5404. ; 167:3, s. 312-8
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to quantify and to determine the distribution of DNA double-strand breaks (DSBs) in human cells irradiated in vitro and to evaluate the relative biological effectiveness (RBE) of the alpha-particle emitter (211)At for DSB induction. The influence of the irradiation temperature on the induction of DSBs was also investigated. Human fibroblasts were irradiated as intact cells with alpha particles from (211)At, (60)Co gamma rays and X rays. The numbers and distributions of DSBs were determined by pulsed-field gel electrophoresis with fragment analysis for separation of DNA fragments in sizes 10 kbp-5.7 Mbp. A non-random distribution was found for DSB induction after irradiation with alpha particles from (211)At, while irradiation with low-LET radiation led to more random distributions. The RBEs for DSB induction were 2.1 and 3.1 for (60)Co gamma rays and X rays as the reference radiation, respectively. In the experiments studying temperature effects, nuclear monolayers were irradiated with (211)At alpha particles or (60)Co gamma rays at 2 degrees C or 37 degrees C and intact cells were irradiated with (211)At alpha particles at the same temperatures. The dose-modifying factor (DMF(temp)) for irradiation of nuclear monolayers at 37 degrees C compared with 2 degrees C was 1.7 for (211)At alpha particles and 1.6 for (60)Co gamma rays. No temperature effect was observed for intact cells irradiated with (211)At. In conclusion, irradiation with alpha particles from (211)At induced two to three times more DSB than gamma rays and X rays.
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| 12. |
- Ebrahimian, T., et al.
(författare)
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Chronic Gamma-Irradiation Induces a Dose-Rate-Dependent Pro-inflammatory Response and Associated Loss of Function in Human Umbilical Vein Endothelial Cells
- 2015
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 183:4, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- A central question in radiation protection research is dose and dose-rate relationship for radiation-induced cardiovascular diseases. The response of endothelial cells to different low dose rates may contribute to help estimate risks for cardiovascular diseases by providing mechanistic understanding. In this study we investigated whether chronic low-dose-rate radiation exposure had an effect on the inflammatory response of endothelial cells and their function. Human umbilical vein endothelial cells (HUVECs) were chronically exposed to radiation at a dose of 1.4 mGy/h or 4.1 mGy/h for 1, 3, 6 or 10 weeks. We determined the pro-inflammatory profile of HUVECs before and during radiation exposure, and investigated the functional consequences of this radiation exposure by measuring their capacity to form vascular networks in matrigel. Expression levels of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1, and the release of pro-inflammatory cytokines such as MCP-1, IL-6 and TNF-alpha were analyzed. When a total dose of 2 Gy was given at a rate of 4.1 mGy/h, we observed an increase in IL-6 and MCP-1 release into the cell culture media, but this was not observed at 1.4 mGy/h. The increase in the inflammatory profile induced at the dose rate of 4.1 mGy/h was also correlated with a decrease in the capacity of the HUVECs to form a vascular network in matrigel. Our results suggest that dose rate is an important parameter in the alteration of HUVEC inflammatory profile and function.
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| 13. |
- Elmroth, Kerstin, 1970, et al.
(författare)
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DNA-incorporated 125I induces more than one double-strand break per decay in mammalian cells.
- 2005
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Ingår i: Radiation research. - 0033-7587 .- 1938-5404. ; 163:4, s. 369-73
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Tidskriftsartikel (refereegranskat)abstract
- The Auger-electron emitter 125I releases cascades of 20 electrons per decay that deposit a great amount of local energy, and for DNA-incorporated 125I, approximately one DNA double-strand break (DSB) is produced close to the decay site. To investigate the potential of 125I to induce additional DSBs within adjacent chromatin structures in mammalian cells, we applied DNA fragment-size analysis based on pulsed-field gel electrophoresis (PFGE) of hamster V79-379A cells exposed to DNA-incorporated 125IdU. After accumulation of decays at -70 degrees C in the presence of 10% DMSO, there was a non-random distribution of DNA fragments with an excess of fragments <0.5 Mbp and the measured yield was 1.6 DSBs/decay. However, since these experiments were performed under high scavenging conditions (DMSO) that reduce indirect effects, the yield in cells exposed to 125IdU under physiological conditions would most likely be even higher. In contrast, using a conventional low-resolution assay without measurement of smaller DNA fragments, the yield was close to one DSB/decay. We conclude that a large fraction of the DSBs induced by DNA-incorporated 125I are nonrandomly distributed and that significantly more than one DSB/decay is induced in an intact cell. Thus, in addition to DSBs produced close to the decay site, DSBs may also be induced within neighboring chromatin fibers, releasing smaller DNA fragments that are not detected by conventional DSB assays.
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| 14. |
- Elmroth, Kerstin, 1970, et al.
(författare)
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Influence of chromatin structure on induction of double-strand breaks in mammalian cells irradiated with DNA-incorporated 125I.
- 2007
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Ingår i: Radiation research. - 0033-7587 .- 1938-5404. ; 168:2, s. 175-82
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Tidskriftsartikel (refereegranskat)abstract
- In this study the induction of double-strand breaks (DSBs) was investigated in Chinese hamster V79-379A cells irradiated with the Auger-electron emitter (125)I incorporated into DNA. The role of chromatin organization was studied by pulse-labeling synchronized cells with (125)IdU before decay accumulation in early or late S phase. Pulsed-field gel electrophoresis and fragment-size analysis were used to quantify the distribution of DNA fragments in irradiated intact cells and naked DNA as well as in DNA from asynchronously labeled cultures in a different scavenging environment. The results show that in intact cells, after accumulation of decays at -70 degrees C in the presence of 10% DMSO, almost four times more DSBs were induced in late S phase compared with early S phase and the fragment distribution was clearly non-random with an excess of fragments <0.2 Mbp. The DSB yield was 0.6 DSB/cell and decay for cells irradiated in early S phase and 2.3 DSBs/cell and decay for cells irradiated in late S phase. When similar experiments were performed on naked genomic DNA or intact cells irradiated with gamma rays, the difference in yield was not as prominent. These data imply a role of chromatin organization in the induction of DSBs by DNA-incorporated (125)I. In summary, the results presented here suggest that the yield of DSBs as well as the fragment distribution induced by (125)IdU decay may vary significantly depending on the chromatin organization during S phase and the labeling procedure used.
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| 15. |
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| 16. |
- Endesfelder, D., et al.
(författare)
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What We Have Learned from RENEB Inter-Laboratory Comparisons Since 2012 With Focus on ILC 2021
- 2023
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 199:6, s. 616-627
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Tidskriftsartikel (refereegranskat)abstract
- Inter-laboratory exercises are important tools within the European network for biological dosimetry and physical retrospective dosimetry (RENEB) to validate and improve the performance of member laboratories and to ensure an operational network with high quality standards for dose estimations in case of a large-scale radiological or nuclear event. In addition to the RENEB inter-laboratory comparison 2021, several inter-laboratory comparisons have been performed in the frame of RENEB for a number of assays in recent years. This publication gives an overview of RENEB inter-laboratory comparisons for biological dosimetry assays in the past and a final summary of the challenges and lessons learnt from the RENEB inter-laboratory comparison 2021. In addition, the dose estimates of all RENEB inter-laboratory comparisons since 2013 that have been conducted for the dicentric chromosome assay, the most established and applied assay, are compared and discussed.
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| 17. |
- Fakir, Hatim, et al.
(författare)
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Clusters of DNA double-strand breaks induced by different doses of nitrogen ions for various LETs : experimental measurements and theoretical analyses
- 2006
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 166:6, s. 917-927
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Tidskriftsartikel (refereegranskat)abstract
- The yields and clustering of DNA double-strand breaks (DSBs) were investigated in normal human skin fibroblasts exposed to gamma rays or to a wide range of doses of nitrogen ions with various linear energy transfers (LETs). Data obtained by pulsed-field gel electrophoresis on the dose and LET dependence of DNA fragmentation were analyzed with the randomly located clusters (RLC) formalism. The formalism considers stochastic clustering of DSBs along a chromosome due to chromatin structure, particle track structure, and multitrack action. The relative biological effectiveness (RBE) for the total DSB yield did not depend strongly on LET, but particles with higher LET produced higher fractions of small DNA fragments, corresponding in the formalism to an increase in the average number of DSBs per DSB cluster. The results are consistent with the idea that DSB clustering along chromosomes is what leads to large RBEs of high-LET radiations for major biological end points. At a given dose, large fragments are less affected by the variability in LET than small fragments, suggesting that the two free ends in large fragments are often produced by two different tracks. The formalism successfully described an extra increase in small DNA fragments as dose increases and a related decrease in large fragments, mainly due to interlacing of DSB clusters produced along a chromosome by different tracks, since interlacing cuts larger DNA fragments into smaller ones.
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| 18. |
- Fessé, Per, et al.
(författare)
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UV-Radiation Response Proteins Reveal Undifferentiated Cutaneous Interfollicular Melanocytes with Hyperradiosensitivity to Differentiation at 0.05 Gy Radiotherapy Dose Fractions.
- 2019
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Ingår i: Radiation research. - 1938-5404 .- 0033-7587. ; 191:1, s. 93-106
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Tidskriftsartikel (refereegranskat)abstract
- To date, the response activated in melanocytes by repeated genotoxic insults from radiotherapy has not been explored. We hypothesized that the molecular pathways involved in the response of melanocytes to ionizing radiation and ultraviolet radiation (UVR) are similar. Skin punch biopsies, not sun-exposed, were collected from prostate cancer patients before, as well as at 1 and 6.5 weeks after daily doses of 0.05-1.1 Gy. Interfollicular melanocytes were identified by ΔNp63- and eosin-periodic acid Schiff staining. Immunohistochemistry and immunofluorescence were performed to detect molecular markers of the melanocyte lineage. Melanocytes were negative for ΔNp63, and the number remained unchanged over the treatment period. At radiation doses as low as 0.05 Gy, melanocytes express higher protein levels of microphthalmia-associated transcription factor (MITF) and Bcl-2. Subsets of MITF- and Bcl-2-negative melanocytes were identified among interfollicular melanocytes in unexposed skin; the cell number in both subsets was reduced after irradiation in a way that indicates low-dose hyperradiosensitivity. A corresponding increase in MITF- and Bcl-2-positive cells was observed. PAX3 and SOX10 co-localized to some extent with MITF in unexposed skin, more so than after radiotherapy. Low doses of ionizing radiation also intensified c-KIT and DCT staining. Nuclear p53 and p21 were undetectable in melanocytes. Apoptosis and proliferation could not be observed. In conclusion, undifferentiated interfollicular melanocytes were identified, and responded with differentiation in a hypersensitive manner at 0.05 Gy doses. Radioresistance regarding cell death was maintained up to fractionated doses of 1.1 Gy, applied for 7 weeks. The results suggest that the initial steps of melanin synthesis are common to ionizing radiation and UVR, and underline the importance of keratinocyte-melanocyte interaction behind hyperpigmentation and depigmentation to radiotherapy.
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| 19. |
- Hauptmann, Monika, et al.
(författare)
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Differential Response and Priming Dose Effect on the Proteome of Human Fibroblast and Stem Cells Induced by Exposure to Low Doses of Ionizing Radiation
- 2016
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 185:3, s. 299-312
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that a mechanistic understanding of the cellular responses to low dose and dose rate may be valuable in reducing some of the uncertainties involved in current risk estimates for cancer- and non-cancer-related radiation effects that are inherited in the linear nothreshold hypothesis. In this study, the effects of low-dose radiation on the proteome in both human fibroblasts and stem cells were investigated. Particular emphasis was placed on examining: 1. the dose-response relationships for the differential expression of proteins in the low-dose range (40-140 mGy) of low-linear energy transfer (LET) radiation; and 2. the effect on differential expression of proteins of a priming dose given prior to a challenge dose (adaptive response effects). These studies were performed on cultured human fibroblasts (VH10) and human adipose-derived stem cells (ADSC). The results from the VH10 cell experiments demonstrated that low-doses of low-LET radiation induced unique patterns of differentially expressed proteins for each dose investigated. In addition, a low priming radiation dose significantly changed the protein expression induced by the subsequent challenge exposure. In the ADSC the number of differentially expressed proteins was markedly less compared to VH10 cells, indicating that ADSC differ in their intrinsic response to low doses of radiation. The proteomic results are further discussed in terms of possible pathways influenced by low-dose irradiation.
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| 20. |
- Jahnson, S, et al.
(författare)
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Reduced mucosal perianastomotic capillary density in rat small intestine with chronic radiation damage.
- 1998
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 150:5, s. 542-8
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Tidskriftsartikel (refereegranskat)abstract
- Anastomoses in an intestine with chronic radiation damage are prone to leakage, possibly due to a reduced blood supply induced by a reduced capillary bed. In an animal model, the numerical capillary density in the perianastomotic area was investigated in intestine with or without chronic radiation damage. A 2-cm segment of rat ileum received a single dose of 21 Gy. Twenty weeks later, when the chronic radiation-induced changes were established, an anastomosis was constructed in this segment and in a corresponding segment in control rats. In situ perfusion fixation of the intestine was done 4 or 7 days after construction of the anastomosis, sections of the intestine were removed surgically, the specimens were embedded in methacrylate plastic and sectioned at 2.5 microm, and capillaries were counted under a light microscope. The circumferential mucosal capillary density was lower in irradiated than in nonirradiated animals at both 4 and 7 days (P < 0.001 and P = 0.04, respectively). This reduction was greater in the mesenteric quadrant than in the other quadrants around the circumference. These results are indicative of a reduced capillary bed in the vicinity of anastomoses in intestine with chronic radiation damage, which might lead to an impeded blood supply and subsequent leakage.
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| 21. |
- Karlsson, Karin H, et al.
(författare)
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Repair of Radiation-Induced Heat-Labile Sites is Independent of DNA-PKcs, XRCC1 and PARP-1
- 2008
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 169:17, s. 506-512
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Tidskriftsartikel (refereegranskat)abstract
- Ionizing radiation induces a variety of different DNA lesions; in addition to the most critical DNA damage, the DSB, numerous base alterations, SSBs and other modifications of the DNA double-helix are formed. When several non-DSB lesions are clustered within a short distance along DNA, or close to a DSB, they may interfere with the repair of DSBs and affect the measurement of DSB induction and repair. We have shown previously that a substantial fraction of DSBs measured by pulsed-field gel electrophoresis (PFGE) are in fact due to heat-labile sites within clustered lesions, thus reflecting an artifact of preparation of genomic DNA at elevated temperature. To further characterize the influence of heat-labile sites on DSB induction and repair, cells of four human cell lines (GM5758, GM7166, M059K, U-1810) with apparently normal DSB rejoining were tested for biphasic rejoining after gamma irradiation. When heat-released DSBs were excluded from the measurements, the fraction of fast rejoining decreased to less than 50% of the total. However, the half-times of the fast (t(1/2) = 7-8 min) and slow (t(1/2) = 2.5 h) DSB rejoining were not changed significantly. At t = 0, the heat-released DSBs accounted for almost 40% of the DSBs, corresponding to 10 extra DSBs per cell per Gy in the initial DSB yield. These heat-released DSBs were repaired within 60-90 min in all cells tested, including M059K cells treated with wortmannin and DNA-PKcs-defective M059J cells. Furthermore, cells lacking XRCC1 or poly(ADP-ribose) polymerase 1 (PARP1) rejoined both total DSBs and heat-released DSBs similarly to normal cells. In summary, the presence of heat-labile sites has a substantial impact on DSB induction and DSB rejoining rates measured by pulsed-field gel electrophoresis, and heat-labile sites repair is independent of DNA-PKcs, XRCC1 and PARP.
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| 22. |
- Lindholm, Carita, et al.
(författare)
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Premature chromosome condensation (PCC) assay for dose assessment in mass casualty accidents
- 2010
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 173:1, s. 71-8
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Tidskriftsartikel (refereegranskat)abstract
- The study was undertaken to establish a dose calibration curve for a practical PCC ring assay and to apply it in a simulated mass casualty accident. The PCC assay was validated against the conventional dicentric assay. A linear relationship was established for PCC rings after (60)Co gamma irradiation with doses up to 20 Gy. In the simulated accident experiment, 62 blood samples were analyzed with both the PCC ring assay and the conventional dicentric assay, applying a triage approach. Samples received various uniform and non-uniform (10-40% partial-body) irradiations up to doses of 13 Gy. The results indicated that both assays yielded good dose estimates for the whole-body exposure scenario, although in the lower-dose range (0-6 Gy) dicentric scoring resulted in more accurate whole-body estimates, whereas PCC rings were better in the high-dose range (>6 Gy). Neither assay was successful in identifying partial-body exposures, most likely due to the low numbers of cells scored in the triage mode. In conclusion, the study confirmed that the PCC ring assay is suitable for use as a biodosimeter after whole-body exposure to high doses of radiation. However, there are limitations for its use in the triage of people exposed to high, partial-body doses.
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| 23. |
- Lundell, Marie, et al.
(författare)
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Breast cancer risk after radiotherapy in infancy : a pooled analysis of two Swedish cohorts of 17,202 infants
- 1999
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Ingår i: Radiation Research. - : Radiation Research Society. - 0033-7587 .- 1938-5404. ; 151:5, s. 626-632
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of breast cancer was studied in a cohort of 17,202 women irradiated for skin hemangioma in infancy at the Radiumhemmet, Stockholm, or the Sahlgrenska University Hospital, Gothenburg. A major part of the cohort had been treated with radium-226 applicators, and the mean absorbed dose to the breasts was 0.29 Gy (range <0.01-35.8 Gy). Two hundred forty-five breast cancers were diagnosed in the cohort during the period 1958-1993, and the standardized incidence ratio (SIR) was 1.20 (95% CI 1.06-1.36). Different dose-response models were tested, and a linear model gave the best fit. Neither age at exposure, breast dose rate, ovarian dose nor time since exposure had any statistically significant modifying effect, and breast dose was the only determinant of risk. The excess relative risk per gray (ERR/Gy) was 0.35 (95% CI 0.18-0.59), which is lower than in most other studies.
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| 24. |
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| 25. |
- Port, M., et al.
(författare)
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RENEB Inter-Laboratory Comparison 2021 : Inter-Assay Comparison of Eight Dosimetry Assays
- 2023
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 199:6, s. 535-555
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Tidskriftsartikel (refereegranskat)abstract
- Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (+/- 0.5 Gy or +/- 1.0 Gy for doses < 2.5 Gy or > 2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (>= 2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.
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| 26. |
- Prasanna, Pataje G. S., et al.
(författare)
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Synopsis of partial-body radiation diagnostic biomarkers and medical management of radiation injury workshop
- 2010
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 173:2, s. 245-53
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Tidskriftsartikel (refereegranskat)abstract
- Radiation exposures from accidents, nuclear detonations or terrorist incidents are unlikely to be homogeneous; however, current biodosimetric approaches are developed and validated primarily in whole-body irradiation models. A workshop was held at the Armed Forces Radiobiology Research Institute in May 2008 to draw attention to the need for partial-body biodosimetry, to discuss current knowledge, and to identify the gaps to be filled. A panel of international experts and the workshop attendees discussed the requirements and concepts for a path forward. This report addresses eight key areas identified by the Workshop Program Committee for future focus: (1) improved cytogenetics, (2) clinical signs and symptoms, (3) cutaneous bioindicators, (4) organ-specific biomarkers, (5) biophysical markers of dose, (6) integrated diagnostic approaches, (7) confounding factors, and (8) requirements for post-event medical follow-up. For each area, the status, advantages and limitations of existing approaches and suggestions for new directions are presented.
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| 27. |
- Rojas, Ana Maria, et al.
(författare)
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Nicotinamide as a repair inhibitor in vivo: single and fractionated X-ray dose studies in mouse skin and kidneys
- 1996
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 145:4, s. 419-431
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of adenosine diphosphoribosyl transferase, like nicotinamide, 3-aminobenzamide and other analogues, can inhibit repair of radiation-induced sublethal and/or potentially lethal damage in some in vitro systems. Therefore, we have tested the effect of nicotinamide on repair parameters in vivo in two rodent normal tissues. In skin, the sensitivity to dose fractionation (1, 2, 5 or 10 X-ray fractions in 5 days) was monitored by defining the alpha/beta ratio in the presence or absence of nicotinamide (0.5 mg g-1) in air or carbogen. Pre- and postirradiation sensitization were investigated using an X-ray schedule of 5 fractions/5 days in carbogen alone or combined with nicotinamide given 1 h before, immediately after or 8 h after irradiation. Also, changes in the steepness of the underlying X-ray survival curve for the target skin clonogens, reflected by a change in the alpha/beta ratio, were investigated using the neutron top-up design. Underlying survival curves for oxygen +/- nicotinamide were obtained over the X-ray dose range 2.5 to 25 Gy, by administering single X-ray doses and following these with single top-up doses of d(4)-Be neutrons. Finally, in mouse kidney, recovery half-times (t1/2) were obtained by determining the time-dependent disappearance of X-ray damage using a split-dose design of two 6-Gy fractions separated by an interval which varied from 0 to 48 h and followed by two top-up doses from a neutron beam. No increase in alpha/beta for epidermal damage was seen with nicotinamide alone and, although sensitization was observed when the drug was given 1 h before irradiation, no postirradiation sensitization was detected. In kidney, there was no significant difference in the proportion of total repairable damage or in the half-life of recovery between treatments given with or without nicotinamide. Therefore, no decrease in normal tissue tolerance should be observed with the use of nicotinamide in clinical radiotherapy resulting either from reduced sparing with dose fractionation or from an increase in residual damage when shortening the interfraction interval. Finally, unless repair of radiation damage in normal tissues in vivo differs markedly from that of tumors, it is unlikely that the large sensitization seen in rodent tumors at 1.5 to 2 Gy per fraction, with carbogen and nicotinamide, can be attributed to nicotinamide acting as a repair inhibitor.
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| 28. |
- Rydberg, B.
(författare)
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The Rate of Strand Separation in Alkali of DNA of Irradiated Mammalian Cells
- 2012
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 178:2, s. AV190-AV197
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Tidskriftsartikel (refereegranskat)abstract
- Rydberg B. The Rate of Strand Separation in Alkali of DNA of Irradiated Mammalian Cells. Radiat. Res. 61, 274-287 (1975). When mammalian cells are treated with alkali of pH at about 12, the cells are lysed and the released DNA starts to uncoil. This process of DNA strand separation is accelerated if the cells have been exposed to ionizing radiation, and the effect is clearly detectable in the dose range 10-100 rads. The rate of strand separation is also influenced by temperature and ionic strength of the alkaline solution. The kinetics of DNA strand separation in alkali is studied for three conditions in terms of ionic strength and temperature, chosen in such a way that the effect of irradiation may conveniently be studied in the dose range 10 rads to 20 krads. The accelerating effect of ionizing radiation on DNA strand separation is probably due to DNA strand breakage and the technique described is thus a sensitive method of studying such damage to DNA. A model for the strand-separation process, based on the assumption that strand breakage causes the accelerating effect, is proposed and found to describe the experimental data adequately.
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| 29. |
- Sangsliwan, Traimate, et al.
(författare)
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The Nucleotide Pool, a Target for Low-Dose gamma-Ray-Induced Oxidative Stress
- 2008
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 170:6, s. 776-783
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress occurs when the generation of reactive oxygen species (ROS) exceeds the cellular antioxidant capacity. The excess ROS react with and modify cellular components Nucleic acid modifications are of principal interest because they may cause mutations. 8-Oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dG) is a mutagenic lesion that can be formed by ROS in DNA as well as in the nucleotide pool. 8-Oxo-dG is removed from the DNA by base excision repair and from the nucleotide pool by the nucleotide sanitization enzyme hMTH1. hMTH1 hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, which is released to the extracellular environment and can serve as a marker of oxidative stress. The aim of this work was to establish the dose-response relationship for radiation-induced extracellular 8-oxo-dG and hMTH1 in the mGy range of gamma rays in three cellular model systems: human whole blood, human fibroblasts and stimulated lymphocytes. Extracellular 8-oxo-dG was analyzed with the use of an ELISA and hMTH 1 by Western blotting. Our results demonstrate that low-dose ionizing radiation induces a stress response that leads to the formation of extracellular 8-oxo-dG and induction of hMTH 1 in all three cellular model systems tested. This suggests that the nucleotide pool is an important target for radiation-induced stress response.
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| 30. |
- Sato, T., et al.
(författare)
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Biological Dose Estimation for Charged-Particle Therapy using an Improved PHITS Code Coupled with a Microdosimetric Kinetic Model
- 2009
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Ingår i: Radiation Research. - 1938-5404 .- 0033-7587. ; 171:1, s. 107-117
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Tidskriftsartikel (refereegranskat)abstract
- Microdosimetric quantities such as lineal energy, y, are better indexes for expressing the RBE of HZE particles in comparison to LET. However, the use of microdosimetric quantities in computational dosimetry is severely limited because of the difficulty in calculating their probability densities in macroscopic matter. We therefore improved the particle transport simulation code PHITS, providing it with the capability of estimating the microdosimetric probability densities in a macroscopic framework by incorporating a mathematical function that can instantaneously calculate the probability densities around the trajectory of HZE particles with a precision equivalent to that of a microscopic track-structure simulation. A new method for estimating biological dose, the product of physical dose and RBE, from charged-particle therapy was established using the improved PHITS coupled with a microdosimetric kinetic model. The accuracy of the biological dose estimated by this method was tested by comparing the calculated physical doses and RBE values with the corresponding data measured in a slab phantom irradiated with several kinds of HZE particles. The simulation technique established in this study will help to optimize the treatment planning of charged-particle therapy, thereby maximizing the therapeutic effect on tumors while minimizing unintended harmful effects on surrounding normal tissues.
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| 31. |
- Sollazzo, Alice, 1981-, et al.
(författare)
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Alpha particles and X-rays interact in inducing DNA damage in U2OS cells
- 2017
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 188:4, s. 400-411
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Tidskriftsartikel (refereegranskat)abstract
- The survivors of atomic bomb explosions in Hiroshima and Nagasaki are monitored for health effect within the Life Span Study (LSS). The LSS results represent the most important source of knowledge about cancer effects of ionizing radiation and they form the basis for the radiation protection system. One uncertainty connected to deriving universal risk factors from these results is related to the problem of mixed radiation qualities. The atomic bomb explosions generated a mixed beam of the sparsely ionizing gamma radiation and densely ionizing neutrons and what is not taken into consideration is the problem of a possible interaction of the two radiation types in inducing biological effects. The existence of such interaction would suggest that the application of risk factors derived from the LSS to predict cancer effects after exposure to pure gamma radiation (such as in the Fukushima prefecture) leads to an overestimation of risk.In order to analyze the possible interaction of radiation types a mixed beam exposure facility was constructed where cells can be exposed to sparsely ionizing X-rays and densely ionizing alpha particles. U2OS cells were used, which are stably transfected with a plasmid coding for the DNA repair gene 53BP1 coupled to a gene coding for the green fluorescent protein GFP. Induction and repair of DNA damage which are known to be related to cancer induction were analyzed. The results suggest that alpha particles and X-rays interact, leading to cellular, and possibly cancer effects not predictable based on assuming simple additivity of the individual mixed beam components.
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| 32. |
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| 33. |
- Turesson, Ingela, et al.
(författare)
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Epidermal Keratinocyte Depletion during Five Weeks of Radiotherapy is Associated with DNA Double-Strand Break Foci, Cell Growth Arrest and Apoptosis: Evidence of Increasing Radioresponsiveness and Lack of Repopulation; The Number of Melanocytes Remains Unchanged
- 2020
-
Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 193:5, s. 481-496
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Tidskriftsartikel (refereegranskat)abstract
- During fractionated radiotherapy, epithelial cell populations are thought to decrease initially, followed by accelerated repopulation to compensate cell loss. However, previous findings in skin with daily 1.1 Gy dose fractions indicate continued and increasing cell depletion. Here we investigated epidermal keratinocyte response with daily 2 Gy fractions as well as accelerated and hypofractionation. Epidermal interfollicular melanocytes were also assessed. Skin-punch biopsies were collected from breast cancer patients before, during and after mastectomy radiotherapy to the thoracic wall with daily 2 Gy fractions for 5 weeks. In addition, 2.4 Gy radiotherapy four times per week and 4 Gy fractions twice per week for 5 weeks, and two times 2 Gy daily for 2.5 weeks, were used. Basal keratinocyte density of the interfollicular epidermis was determined and immunostainings of keratinocytes for DNA double-strand break (DSB) foci, growth arrest, apoptosis and mitosis were quantified. In addition, interfollicular melanocytes were counted. Initially minimal keratinocyte loss was observed followed by pronounced depletion during the second half of treatment and full recovery at 2 weeks post treatment. DSB foci per cell peaked towards the end of treatment. p21-stained cell counts increased during radiotherapy, especially the second half. Apoptotic frequency was low throughout radiotherapy but increased at treatment end. Mitotic cell count was significantly suppressed throughout radiotherapy and did not recover during weekend treatment gaps, but increased more than threefold compared to unexposed skin 2 weeks post-radiotherapy. The number of melanocytes remained constant over the study period. Germinal keratinocyte loss rate increased gradually during daily 2 Gy fractions for 5 weeks, and similarly for hypofractionation. DSB foci number after 2 Gy irradiation revealed an initial radioresistance followed by increasing radiosensitivity. Growth arrest mediated by p21 strongly suggests that cells within or recruited into the cell cycle during treatment are at high risk of loss and do not contribute significantly to repopulation. It is possible that quiescent (G0) cells at treatment completion accounted for the accelerated post-treatment repopulation. Recent knowledge of epidermal tissue regeneration and cell cycle progression during genotoxic and mitogen stress allows for a credible explanation of the current finding. Melanocytes were radioresistant regarding cell depletion. © 2020 by Radiation Research Society. All rights of reproduction in any form reserved.
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| 34. |
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| 35. |
- Veiga, Lene H. S., et al.
(författare)
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A Pooled Analysis of Thyroid Cancer Incidence Following Radiotherapy for Childhood Cancer
- 2012
-
Ingår i: Radiation Research. - Lawrence : Radiation Research Society. - 0033-7587 .- 1938-5404. ; 178:4, s. 365-376
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Tidskriftsartikel (refereegranskat)abstract
- Childhood cancer five-year survival now exceeds 70-80%. Childhood exposure to radiation is a known thyroid carcinogen; however, data are limited for the evaluation of radiation dose-response at high doses, modifiers of the dose-response relationship and joint effects of radiotherapy and chemotherapy. To address these issues, we pooled two cohort and two nested case-control studies of childhood cancer survivors including 16,757 patients, with 187 developing primary thyroid cancer. Relative risks (RR) with 95% confidence intervals (CI) for thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin were 3.25 (0.9-14.9), 4.5 (1.4-17.8) and 3.2 (0.8-10.4), respectively, in patients without radiotherapy, and declined with greater radiation dose (RR trends, P = 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs increased approximately linearly for <10 Gy, leveled off at 10-15-fold for 10-30 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95% CI: 8.0-24.0). Dose-related excess RRs increased with decreasing age at exposure (P < 0.01), but did not vary with attained age or time-since-exposure, remaining elevated 25+ years after exposure. Gender and number of treatments did not modify radiation effects. Thyroid cancer risks remained elevated many decades following radiotherapy, highlighting the need for continued follow up of childhood cancer survivors. (C) 2012 by Radiation Research Society
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| 36. |
- Veiga, Lene H. S., et al.
(författare)
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Thyroid Cancer after Childhood Exposure to External Radiation : An Updated Pooled Analysis of 12 Studies
- 2016
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 185:5, s. 473-484
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Tidskriftsartikel (refereegranskat)abstract
- Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation.
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| 37. |
- Villegas, Fernanda, 1983-, et al.
(författare)
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Target size variation in microdosimetric distributions and its impact on the linear-quadratic parameterization of cell survival.
- 2018
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 190, s. 504-512
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Tidskriftsartikel (refereegranskat)abstract
- The linear-quadratic (LQ) parameterization of survival fraction SF(D) inherently assumes that all cells in a population get the same dose D, albeit the distribution of specific energy z over the individual cells f(z,D) can be very wide. From these microdosimetric distributions, which are target size dependent, we estimate the size of the cellular sensitive volume by analysing its influence on the LQ parameterization of cell survival. A Monte Carlo track structure code was used to simulate detailed tracks from a 60Co source as well as proton and carbon ions of various energies. From these tracks, f(z,D) distributions were calculated for spherical targets with diameters ranging from 10 nm to 12 µm. A cell survival function based on f(z,D) was fitted to published experimental LQ α values, revealing an intrinsic limitation that target size imposes on the usage of f(z,D) to describe the linear term of the LQ parameterization. The results indicate that such threshold volume arises naturally from the relationship between the particle´s probability of no-hit and the probability of cell survival. Further analysis led to the proposal of a radiobiological property yf,MID, defined as the mean lineal energy corresponding to the target size that allows equivalence between the mean inactivation dose (MID) and the mean specific energy z1. The fact that z1 is an increasing continuous function of target size within the range of biological targets of interest in radiobiology, ensures the uniqueness of yf,MID for any radiation quality, thus, its potential usefulness in modelling. In conclusion, an accurate estimation of such threshold volumes may be useful for improving modelling of cell survival curves.
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| 38. |
- Waldeland, Einar, et al.
(författare)
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Radical formation in lithium formate EPR dosimeters after irradiation with protons and nitrogen ions
- 2010
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 174:2, s. 251-257
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Tidskriftsartikel (refereegranskat)abstract
- Radical formation in polycrystalline lithium formate monohydrate after irradiation with gamma rays, protons and nitrogen ions at room temperature was studied by continuous-wave electron paramagnetic resonance (EPR) spectroscopy. The linear energy transfer (LET) of the various radiation beams was 0.2, 0.7-3.9 and 110-164 keV/microm for gamma rays, protons and nitrogen ions, respectively. Doses between 5 and 20 Gy were given. The EPR reading (the area under the EPR absorption resonance) increased linearly with dose for all types of radiation. As the LET increased, the relative effectiveness (the EPR reading per dose relative to that for gamma rays) decreased, while the EPR line width increased. Track structure theory and modeling of detector effectiveness predicted the dosimeter response observed after proton and nitrogen-ion irradiation. A semi-empirical line broadening model including dipolar spin-spin interactions was developed that explained the dependence of the line width on LET. The findings indicate that the local radical density in lithium formate is increased after high-LET irradiation.
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| 39. |
- Waldner, L., et al.
(författare)
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The 2019-2020 EURADOS WG10 and RENEB Field Test of Retrospective Dosimetry Methods in a Small-Scale Incident Involving Ionizing Radiation
- 2021
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 195:3, s. 253-264
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Tidskriftsartikel (refereegranskat)abstract
- With the use of ionizing radiation comes the risk of accidents and malevolent misuse. When unplanned exposures occur, there are several methods which can be used to retrospectively reconstruct individual radiation exposures; biological methods include analysis of aberrations and damage of chromosomes and DNA, while physical methods rely on luminescence (TL/OSL) or EPR signals. To ensure the quality and dependability of these methods, they should be evaluated under realistic exposure conditions. In 2019, EURADOS Working Group 10 and RENEB organized a field test with the purpose of evaluating retrospective dosimetry methods as carried out in potential real-life exposure scenarios. A 1.36 TBq 192Ir source was used to irradiate anthropomorphic phantoms in different geometries at doses of several Gy in an outdoor open-air geometry. Materials intended for accident dosimetry (including mobile phones and blood) were placed on the phantoms together with reference dosimeters (LiF, NaCl, glass). The objective was to estimate radiation exposures received by individuals as measured using blood and fortuitous materials, and to evaluate these methods by comparing the estimated doses to reference measurements and Monte Carlo simulations. Herein we describe the overall planning, goals, execution and preliminary outcomes of the 2019 field test. Such field tests are essential for the development of new and existing methods. The outputs from this field test include useful experience in terms of planning and execution of future exercises, with respect to time management, radiation protection, and reference dosimetry to be considered to obtain relevant data for analysis.
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| 40. |
- Wedenberg, Mina, et al.
(författare)
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Analytical description of the LET dependence of cell survival using the repairable-conditionally repairable damage model
- 2010
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 96, s. S534-S534
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Tidskriftsartikel (refereegranskat)abstract
- In light-ion radiation therapy, both the dose and the local energy spectrum, which is often characterized with the linear energy transfer (LET), must be considered. In treatment optimization, it is advantageous to use a radiobiological model that analytically accounts for both dose and LET for the ion type of interest. With such a model the biological effect can also be estimated for dose and LET combinations for which there are no observations in the underlying experimental data. In this study, the repairable-conditionally repairable (RCR) damage model was extended by expressing its parameters as functions of LET to provide a radiobiological model that accounts for both the dose and the LET for a given ion type and cell line. This LET-parameterized RCR model was fitted to published cell survival data for HSG and V79 cells irradiated with carbon ions and for T1 cells irradiated with helium ions. To test the robustness of the model, fittings to only a subset of the data were performed. Good agreement with the cell survival data was obtained, including survival data for LET values not used for model fitting, opening up the possibility of using the model in treatment planning for light ions.
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| 41. |
- Wiklund, Kristin, 1976-, et al.
(författare)
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Radial secondary electron dose profiles and biological effects in light-ion beams based on analytical and Monte Carlo calculations using distorted wave cross sections
- 2008
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 170:1, s. 83-92
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Tidskriftsartikel (refereegranskat)abstract
- To speed up dose calculation, an analytical pencil-beam method has been developed to calculate the mean radial dose distributions due to secondary electrons that are set in motion by light ions in water. For comparison, radial dose profiles calculated using a Monte Carlo technique have also been determined. An accurate comparison of the resulting radial dose profiles of the Bragg peak for (1)H(+), (4)He(2+) and (6)Li(3+) ions has been performed. The double differential cross sections for secondary electron production were calculated using the continuous distorted wave-eikonal initial state method (CDW-EIS). For the secondary electrons that are generated, the radial dose distribution for the analytical case is based on the generalized Gaussian pencil-beam method and the central axis depth-dose distributions are calculated using the Monte Carlo code PENELOPE. In the Monte Carlo case, the PENELOPE code was used to calculate the whole radial dose profile based on CDW data. The present pencil-beam and Monte Carlo calculations agree well at all radii. A radial dose profile that is shallower at small radii and steeper at large radii than the conventional 1/r(2) is clearly seen with both the Monte Carlo and pencil-beam methods. As expected, since the projectile velocities are the same, the dose profiles of Bragg-peak ions of 0.5 MeV (1)H(+), 2 MeV (4)He(2+) and 3 MeV (6)Li(3+) are almost the same, with about 30% more delta electrons in the sub keV range from (4)He(2+)and (6)Li(3+) compared to (1)H(+). A similar behavior is also seen for 1 MeV (1)H(+), 4 MeV (4)He(2+) and 6 MeV (6)Li(3+), all classically expected to have the same secondary electron cross sections. The results are promising and indicate a fast and accurate way of calculating the mean radial dose profile.
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| 42. |
- Zackrisson, Björn, 1954-, et al.
(författare)
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Relative biological effectiveness of 50-MV X-rays on jejunal crypt survival in vivo
- 1992
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Ingår i: Radiation Research. - Oak Brook, IL 60521 USA : Radiation Research Society. - 0033-7587 .- 1938-5404. ; 132:1, s. 112-114
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Tidskriftsartikel (refereegranskat)abstract
- Earlier in vitro studies of relative biological effectiveness (RBE) of 50-MV X rays show an RBE of approximately 1.1 compared to 4 MV. No difference in RBE has been found for 20-MV X rays or 50-MeV electrons. The higher RBE for 50 MV can be explained to some extent by the small high linear energy transfer contribution from photonuclear reactions at high X-ray energies. To investigate the validity of the results in vitro, a study of the RBE of 50-MV X rays has been performed in vivo using the jejunal crypt microcolony assay in mice. The reference radiation used in this case was 20-MV X rays. The results confirm the earlier in vitro studies. The RBE for 50-MV X rays was estimated to be 1.06, calculated as the ratio between the slopes of the response curves.
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| 43. |
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| 44. |
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| 45. |
- Adrian, Gabriel, et al.
(författare)
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Rescue Effect Inherited in Colony Formation Assays Affects Radiation Response
- 2018
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Ingår i: Radiation Research. - 0033-7587. ; 189:1, s. 44-52
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that nonirradiated cells can exhibit radiation damage (bystander effect), and recent findings have shown that nonirradiated cells may help protect irradiated cells (rescue effect). These findings call into question the traditional view of radiation response: cells cannot be envisioned as isolated units. Here, we investigated traditional colony formation assays to determine if they also comprise cellular communication affecting the radiation response, using colony formation assays with varying numbers of cells, modulated beam irradiation and media transfer. Our findings showed that surviving fraction gradually increased with increasing number of irradiated cells. Specifically, for DU-145 human prostate cancer cells, surviving fraction increased 1.9-to-4.1-fold after 5-12 Gy irradiation; and for MM576 human melanoma cells, surviving fraction increased 1.9-fold after 5 Gy irradiation. Furthermore, increased surviving fraction was evident after modulated beam irradiation, where irradiated cells could communicate with nonirradiated cells. Media from dense cell culture also increased surviving fraction. The results suggest that traditional colony formation assays comprise unavoidable cellular communication affecting radiation outcome and the shape of the survival curve. We also propose that the increased in-field surviving fraction after modulated beam irradiation is due to the same effect.
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| 46. |
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