| 1. |
- Andreassi, Maria Grazia, et al.
(författare)
-
A Longitudinal Study of Individual Radiation Responses in Pediatric Patients Treated with Proton and Photon Radiotherapy, and Interventional Cardiology : Rationale and Research Protocol of the HARMONIC Project
- 2023
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24:9, s. 8416-
-
Tidskriftsartikel (refereegranskat)abstract
- The Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy (photon and proton) in Pediatrics (HARMONIC) is a five-year project funded by the European Commission that aimed to improve the understanding of the long-term ionizing radiation (IR) risks for pediatric patients. In this paper, we provide a detailed overview of the rationale, design, and methods for the biological aspect of the project with objectives to provide a mechanistic understanding of the molecular pathways involved in the IR response and to identify potential predictive biomarkers of individual response involved in long-term health risks. Biological samples will be collected at three time points: before the first exposure, at the end of the exposure, and one year after the exposure. The average whole-body dose, the dose to the target organ, and the dose to some important out-of-field organs will be estimated. State-of-the-art analytical methods will be used to assess the levels of a set of known biomarkers and also explore high-resolution approaches of proteomics and miRNA transcriptomes to provide an integrated assessment. By using bioinformatics and systems biology, biological pathways and novel pathways involved in the response to IR exposure will be deciphered.
|
|
| 2. |
- Sangsuwan, Traimate, 1981-, et al.
(författare)
-
Oxidative Stress Levels and DNA Repair Kinetics in Senescent Primary Human Fibroblasts Exposed to Chronic Low Dose Rate of Ionizing Radiation
- 2023
-
Ingår i: Frontiers in Bioscience Landmark. - 2768-6701. ; 28:11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure to low dose rate (LDR) radiation may accelerate aging processes. Previously, we identified numerous LDR-induced pathways involved in oxidative stress (OS) and antioxidant systems, suggesting that these pathways protect against premature senescence (PS). This study aimed to investigate if there are differences between young replicative senescent (RS) and PS cells considering DNA repair kinetics, OS, and DNA damage localized in the telomeres. Methods: We established PS cells by culturing and passaging young primary fibroblasts exposed to LDR. Then, RS cells were established by culturing and passaging young fibroblasts until they stopped proliferating. Senescence was characterized by analyzing telomere length and senescence-associated β-galactosidase (SA-β-gal) staining. DNA damage and repair were evaluated with γH2AX foci formation; telomere identification was carried out using the fluorescence in situ hybridization (FISH) probe; and oxidative stress was assessed by measuring 8-oxo-dG in the medium. Results: The data indicate the following: young cells have a better ability to cope with LDR-induced oxidative stress; RS and PS have higher steady-state levels of DNA damage; RS have slower DNA repair kinetics; and PS/RS have elevated levels of telomeric DNA damage. Conclusion: Our main conclusion is that PS and RS differ regarding DNA repair kinetics and SA-β-gal levels.
|
|
| 3. |
- Babini, Gabriele, et al.
(författare)
-
A systems radiation biology approach to unravel the role of chronic low-dose-rate gamma-irradiation in inducing premature senescence in endothelial cells
- 2022
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:3
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeThe aim of this study was to explore the effects of chronic low-dose-rate gamma-radiation at a multi-scale level. The specific objective was to obtain an overall view of the endothelial cell response, by integrating previously published data on different cellular endpoints and highlighting possible different mechanisms underpinning radiation-induced senescence.Materials and methodsDifferent datasets were collected regarding experiments on human umbilical vein endothelial cells (HUVECs) which were chronically exposed to low dose rates (0, 1.4, 2.1 and 4.1 mGy/h) of gamma-rays until cell replication was arrested. Such exposed cells were analyzed for different complementary endpoints at distinct time points (up to several weeks), investigating cellular functions such as proliferation, senescence and angiogenic properties, as well as using transcriptomics and proteomics profiling. A mathematical model was proposed to describe proliferation and senescence.ResultsSimultaneous ceasing of cell proliferation and senescence onset as a function of time were well reproduced by the logistic growth curve, conveying shared equilibria between the two endpoints. The combination of all the different endpoints investigated highlighted a dose-dependence for prematurely induced senescence. However, the underpinning molecular mechanisms appeared to be dissimilar for the different dose rates, thus suggesting a more complex scenario.ConclusionsThis study was conducted integrating different datasets, focusing on their temporal dynamics, and using a systems biology approach. Results of our analysis highlight that different dose rates have different effects in inducing premature senescence, and that the total cumulative absorbed dose also plays an important role in accelerating endothelial cell senescence.
|
|
| 4. |
- Bråkenhielm, Carl-Reinhold
(bidragsgivare, creator_code:cre_t)
-
Kunskapsläget på kärnavfallsområdet 2022 : Samhället, tekniken och etiken
- 2022
-
Rapport (populärvet., debatt m.m.)abstract
- Kärnavfallsrådet (Statens råd för kärnavfallsfrågor) är en tvärvetenskaplig kommitté som har i uppdrag att ge regeringen råd i frågor om använt kärnbränsle, kärnavfall och rivning av kärntekniska anläggningar, (M 1992:A Kärnavfallsrådet. Dir. 2018:18). I februari vartannat år ger Kärnavfallsrådet sin självständiga bedömning av det aktuella läget inom kärnavfallsområdet. Bedömningen presenteras i form av en kunskapslägesrapport. Syftet med rapporten är att upp-märksamma och beskriva frågor som Kärnavfallsrådet anser viktiga och att redogöra för rådets synpunkter i dessa. Kärnavfallsrådet överlämnar härmed till regeringen årets kunskapslägesrapport SOU 2022:7 Kunskapsläget på kärnavfallsområdet 2022 – Samhället, tekniken och etiken.Bakom denna rapport står samtliga ledamöter och sakkunniga i Kärnavfallsrådet. Kärnavfallsrådets vetenskapliga sekreterare Johanna Swedin har varit projektledare för arbetet med kunskapslägesrapporten.Rapporterna om kunskapsläget på kärnavfallsområdet åren 1998, 2001, 2004, 2007, 2010, 2011, 2012, 2013, 2014, 2015, 2016, 2017, 2018 och 2020 finns även tillgängliga i en engelsk version. Rådet kommer att publicera en engelsk översättning av årets rapport under våren 2022.
|
|
| 5. |
|
|
| 6. |
- Drobin, Kimi, et al.
(författare)
-
Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer
- 2020
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:3
-
Tidskriftsartikel (refereegranskat)abstract
- Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear during or long time after finishing radiotherapy and depending on the patient's radiosensitivity. Currently, there is no assay available that can reliably predict the individual's response to radiotherapy. We profiled two study sets from breast (n = 29) and head-and-neck cancer patients (n = 74) that included radiosensitive patients and matched radioresistant controls. We studied 55 single nucleotide polymorphisms (SNPs) in 33 genes by DNA genotyping and 130 circulating proteins by affinity-based plasma proteomics. In both study sets, we discovered several plasma proteins with the predictive power to find radiosensitive patients (adjusted p < 0.05) and validated the two most predictive proteins (THPO and STIM1) by sandwich immunoassays. By integrating genotypic and proteomic data into an analysis model, it was found that the proteins CHIT1, PDGFB, PNKD, RP2, SERPINC1, SLC4A, STIM1, and THPO, as well as the VEGFA gene variant rs69947, predicted radiosensitivity of our breast cancer (AUC = 0.76) and head-and-neck cancer (AUC = 0.89) patients. In conclusion, circulating proteins and a SNP variant of VEGFA suggest that processes such as vascular growth capacity, immune response, DNA repair and oxidative stress/hypoxia may be involved in an individual's risk of experiencing radiation-induced toxicity.
|
|
| 7. |
- Jönsson, K. Ingemar, et al.
(författare)
-
Environmental adaptations : radiation tolerance
- 2019
-
Ingår i: Water bears. - Lund : Springer. ; , s. 311-330
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Several studies in different species have documented that tardigrades are among the most radiation-tolerant animals on Earth, surviving doses of ionizing radiation on the order of kGy. Both low-LET and high-LET radiation have been used with no apparent differences in the tolerance of the animals. Tolerance to ionizing radiation in tardigrades also seems to be independent of whether the animal has entered a dry anhydrobiotic state or is hydrated with normal activity. However, when exposed to UV radiation, desiccated tardigrades show a higher tolerance than hydrated animals. Recent studies in several species have shown that tardigrade embryos have considerably lower tolerance to ionizing radiation compared to adults, and embryos in the early stage of development are clearly more sensitive to radiation than those in the late developmental stage. The molecular mechanisms behind radiation tolerance in tardigrades are still largely unclear, but available evidence suggests that mechanisms related to both the avoidance of DNA damage and the repair of damage are involved.
|
|
| 8. |
- Wojcik, Andrzej, et al.
(författare)
-
Radiation protection biology then and now
- 2019
-
Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 95:7, s. 841-850
-
Forskningsöversikt (refereegranskat)abstract
- Purpose: Radiation biology is a branch of the radiation research field which focuses on studying radiation effects in cells and organisms. Radiation can be used in biological investigations for two, mutually non-exclusive reasons: (1) to study biological processes by perturbing their functioning (qualitative approach) and (2) to assess consequences of radiation-induced damage (quantitative approach). While the former approach has a basic research character, the latter has an applied character that is driven by needs of medical applications and radiological protection. Radiation protection biology is defined in the sense of the second approach. The aim of the article is to provide a historical review of how radiation protection biology developed and how it influences radiological protection.Conclusions: While radiobiological investigations started immediately after the discovery of X-rays, the qualitative approach dominated until the end of World War II. After 1945, the nuclear weapons race and nuclear energy programs initiated quantitative radiobiological research. Radiation protection biology does not provide results from which radiation risks can be directly derived. Rather, it provides data that is necessary for understanding the nature of risks. Most recent years have seen, especially in Europe, a growing interest in coordinated studies on the effects of low radiation doses.
|
|
| 9. |
- Kreuzer, M., et al.
(författare)
-
Multidisciplinary European Low Dose Initiative (MELODI) : strategic research agenda for low dose radiation risk research
- 2018
-
Ingår i: Radiation and Environmental Biophysics. - : Springer Science and Business Media LLC. - 0301-634X .- 1432-2099. ; 57:1, s. 5-15
-
Forskningsöversikt (refereegranskat)abstract
- MELODI (Multidisciplinary European Low Dose Initiative) is a European radiation protection research platform with focus on research on health risks after exposure to low-dose ionising radiation. It was founded in 2010 and currently includes 44 members from 18 countries. A major activity of MELODI is the continuous development of a long-term European Strategic Research Agenda (SRA) on low-dose risk for radiation protection. The SRA is intended to identify priorities for national and European radiation protection research programs as a basis for the preparation of competitive calls at the European level. Among those key priorities is the improvement of health risk estimates for exposures close to the dose limits for workers and to reference levels for the population in emergency situations. Another activity of MELODI is to ensure the availability of European key infrastructures for research activities, and the long-term maintenance of competences in radiation research via an integrated European approach for training and education. The MELODI SRA identifies three key research topics in low dose or low dose-rate radiation risk research: (1) dose and dose rate dependence of cancer risk, (2) radiation-induced non-cancer effects and (3) individual radiation sensitivity. The research required to improve the evidence base for each of the three key topics relates to three research lines: (1) research to improve understanding of the mechanisms contributing to radiogenic diseases, (2) epidemiological research to improve health risk evaluation of radiation exposure and (3) research to address the effects and risks associated with internal exposures, differing radiation qualities and inhomogeneous exposures. The full SRA and associated documents can be downloaded from the MELODI website (http://www.melodi-online.eu/sra.html).
|
|
| 10. |
- McLean, Angela R., et al.
(författare)
-
A restatement of the natural science evidence base concerning the health effects of low-level ionizing radiation
- 2017
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 284:1862
-
Forskningsöversikt (refereegranskat)abstract
- Exposure to ionizing radiation is ubiquitous, and it is well established that moderate and high doses cause ill-health and can be lethal. The health effects of low doses or low dose-rates of ionizing radiation are not so clear. This paper describes a project which sets out to summarize, as a restatement, the natural science evidence base concerning the human health effects of exposure to low-level ionizing radiation. A novel feature, compared to other reviews, is that a series of statements are listed and categorized according to the nature and strength of the evidence that underpins them. The purpose of this restatement is to provide a concise entree into this vibrant field, pointing the interested reader deeper into the literature when more detail is needed. It is not our purpose to reach conclusions on whether the legal limits on radiation exposures are too high, too low or just right. Our aim is to provide an introduction so that non-specialist individuals in this area (be they policy-makers, disputers of policy, health professionals or students) have a straightforward place to start. The summary restatement of the evidence and an extensively annotated bibliography are provided as appendices in the electronic supplementary material.
|
|
