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Biomarkers of Atherosclerotic Vascular Disease in Workers Chronically Exposed to Ionizing Radiation.Health Physics Aug 2021It is well established that cohorts of individuals exposed to ionizing radiation demonstrate increased risks of cardio- and cerebrovascular diseases. However, mechanisms...
It is well established that cohorts of individuals exposed to ionizing radiation demonstrate increased risks of cardio- and cerebrovascular diseases. However, mechanisms of these radiation-induced diseases developing in individuals exposed to ionizing radiation remain unclear. To identify biomarkers of the atherosclerotic vessel damage in workers chronically exposed to ionizing radiation, this study considered 49 workers of the Russian nuclear production facility-the Mayak Production Association (mean age of 68.73 ± 6.92 years)-and 38 unexposed individuals (mean age of 68.84 ± 6.20 y) who had never been exposed to ionizing radiation (control). All workers were chronically exposed to combined radiation (external gamma rays and internal alpha particles). The mean cumulative liver absorbed dose from external gamma-ray exposure was 0.18 ± 0.12 Gy; the mean cumulative liver absorbed dose from internal alpha-particles was 0.14 ± 0.21 Gy. Levels of biomarkers in blood serum of the study participants were measured using the ELISA method. Elevated levels of apolipoprotein B, superoxide dismutase, monocyte chemoattractant protein 1, vascular cell adhesion protein 1, and a decreased level of endothelin-1 were observed in blood serum of Mayak PA workers chronically exposed to combined radiation compared to control individuals. A significant positive correlation was demonstrated between the vascular cell adhesion protein 1 level and cumulative liver absorbed doses from external gamma radiation and internal alpha radiation. Findings of the study suggest that molecular changes in blood of individuals occupationally exposed to ionizing radiation (combined internal exposure to alpha particles and external exposure to gamma rays) may indicate dyslipidemia, oxidative stress, inflammation, and endothelial dysfunction involved in atherosclerosis development.
Topics: Alpha Particles; Atherosclerosis; Biomarkers; Gamma Rays; Humans; Occupational Exposure; Radiation, Ionizing; Russia
PubMed: 33867435
DOI: 10.1097/HP.0000000000001416 -
Seminars in Nuclear Medicine Mar 2020As a treatment modality that is fundamentally different from other therapies against cancer, radiopharmaceutical therapy with alpha-particle emitters has drawn the... (Review)
Review
As a treatment modality that is fundamentally different from other therapies against cancer, radiopharmaceutical therapy with alpha-particle emitters has drawn the attention of the therapy community and also the biopharmaceutical industry. Alpha-particles cause a preponderance of complex DNA double-strand breaks (DSBs). This provides an opportunity to either enhance cell kill by using DNA DSB repair inhibitors or identify patients who are likely to be high responders to alpha-emitter RPT. The short-range and high potency of alpha-particles requires special dosimetry considerations. These are reviewed in light of recent updates to the phantoms and associated dosimetric quantities used for dosimetry calculations. A formalism for obtaining the necessary microscale pharmacokinetic information from patient nuclear medicine imaging is presented. Alpha-emitter based radiopharmaceutical therapy is an exciting cancer therapy modality that is being revisited. Further development of imaging and dosimetric methods specific to alpha-particle emitters, coupled with standardization of the methods and rigorous evidence that dosimetry applied to alphaRPT improves patient care are needed moving forward.
Topics: Alpha Particles; Humans; Radiobiology; Radiometry; Radiopharmaceuticals
PubMed: 32172797
DOI: 10.1053/j.semnuclmed.2019.11.002 -
International Journal of Radiation... Apr 2020The article reports on a comparative analysis of biological specimens of lung tissues collected from workers with pulmonary fibrosis induced by internal exposure to...
The article reports on a comparative analysis of biological specimens of lung tissues collected from workers with pulmonary fibrosis induced by internal exposure to plutonium alpha-particles (plutonium-induced pulmonary fibrosis [PuPF]) and with etiologically different pulmonary fibrosis (non-PuPF) that developed as an outcome of a chronic obstructive pulmonary disease (COPD). To perform histological examinations, lung tissues were sampled during autopsy. Six samples of various lung regions (the apical region, the lingula of the left lung and the inferior lobe) were collected from each donor. The resected tissue samples were fixed in 10% neutral-buffered formalin during 24 h and embedded into paraffin blocks (FFPE). FFPE blocks with lung tissue specimens collected from 56 workers with PuPF, 34 workers with non-PuPF and 35 workers without any lung disease were used in the study. To perform microscopic examination, lung tissue specimens were hematoxylin and eosin stained. To examine the connective-tissue scaffold of lung stroma and identify foci of pulmonary fibrosis, the cut sections of paraffin blocks were stained by Van Gizon's method (to assess the total volume of fibrosis-affected tissues), Gomori's technique (to define the reticular scaffold of lung stroma) and Weigert's technique (to examine elastic fibers). Morphological patterns of all biological specimens were studied using immunohistochemistry. To fit the empirical data, the Weibull's model was used. The study found qualitative and quantitative morphological features specific for PuPF compared to non-PuPF. The study demonstrated that hyper-production of collagen type V plays a key role in PuPF. The collagen type V content in fibrotic foci in lung tissue specimens from workers with PuPF was found to be increased.
Topics: Adult; Aged; Aged, 80 and over; Alpha Particles; Collagen; Female; Humans; Male; Middle Aged; Occupational Diseases; Pulmonary Fibrosis; Radiation Injuries; Transforming Growth Factor beta1
PubMed: 31985334
DOI: 10.1080/09553002.2020.1721601 -
Radiation and Environmental Biophysics Nov 2022Heterogeneity of dose distribution has been shown at different spatial scales in diagnostic nuclear medicine. In cancer treatment using new radiopharmaceuticals with... (Review)
Review
Heterogeneity of dose distribution has been shown at different spatial scales in diagnostic nuclear medicine. In cancer treatment using new radiopharmaceuticals with alpha-particle emitters, it has shown an extensive degree of dose heterogeneity affecting both tumour control and toxicity of organs at risk. This review aims to provide an overview of generalized internal dosimetry in nuclear medicine and highlight the need of consideration of the dose heterogeneity within organs at risk. The current methods used for patient dosimetry in radiopharmaceutical therapy are summarized. Bio-distribution and dose heterogeneities of alpha-particle emitting pharmaceutical Ra (Xofigo) within bone tissues are presented as an example. In line with the strategical research agendas of the Multidisciplinary European Low Dose Initiative (MELODI) and the European Radiation Dosimetry Group (EURADOS), future research direction of pharmacokinetic modelling and dosimetry in patient radiopharmaceutical therapy are recommended.
Topics: Humans; Radiopharmaceuticals; Radioisotopes; Alpha Particles; Radiometry; Neoplasms
PubMed: 36239799
DOI: 10.1007/s00411-022-01000-5 -
Current Radiopharmaceuticals Oct 2011Radioimmunotherapy based on α-particle emitters has excellent properties as a treatment against micrometastatic and disseminated cancers because of the short path... (Review)
Review
Radioimmunotherapy based on α-particle emitters has excellent properties as a treatment against micrometastatic and disseminated cancers because of the short path length (50 - 80 μm) and high linear energy transfer (∼ 100 keV/ μm). Alpha-particles produce clustered DNA double-strand breaks and highly reactive hydroxyl radicals when hitting biological tissue. Hence, targeted α-particle therapy offers the potential of selective tumor cell killing with low damage to surrounding normal tissue. The ideal applications for targeted α-therapy are in treating neoplastic cells in circulation or when cancer cells are present as free-floating cells or spread along compartment walls. This review will provide a brief overview of the most promising radionuclides for targeted α-therapy and compare their relative biological effectiveness (RBE) and normal tissue toxicity.
Topics: Alpha Particles; Animals; Humans; Immunoconjugates; Neoplasms; Relative Biological Effectiveness
PubMed: 22202154
DOI: 10.2174/1874471011104040321 -
BMC Medical Genomics Jul 2014The threat of a terrorist-precipitated nuclear event places humans at danger for radiological exposures. Isotopes which emit alpha (α)-particle radiation pose the...
BACKGROUND
The threat of a terrorist-precipitated nuclear event places humans at danger for radiological exposures. Isotopes which emit alpha (α)-particle radiation pose the highest risk. Currently, gene expression signatures are being developed for radiation biodosimetry and triage with respect to ionizing photon radiation. This study was designed to determine if similar gene expression profiles are obtained after exposures involving α-particles.
METHODS
Peripheral blood mononuclear cells (PBMCs) were used to identify sensitive and robust gene-based biomarkers of α-particle radiation exposure. Cells were isolated from healthy individuals and were irradiated at doses ranging from 0-1.5 Gy. Microarray technology was employed to identify transcripts that were differentially expressed relative to unirradiated cells 24 hours post-exposure. Statistical analysis identified modulated genes at each of the individual doses.
RESULTS
Twenty-nine genes were common to all doses with expression levels ranging from 2-10 fold relative to control treatment group. This subset of genes was further assessed in independent complete white blood cell (WBC) populations exposed to either α-particles or X-rays using quantitative real-time PCR. This 29 gene panel was responsive in the α-particle exposed WBCs and was shown to exhibit differential fold-changes compared to X-irradiated cells, though no α-particle specific transcripts were identified.
CONCLUSION
Current gene panels for photon radiation may also be applicable for use in α-particle radiation biodosimetry.
Topics: Alpha Particles; DNA Damage; Dose-Response Relationship, Radiation; Female; Genomics; Humans; Leukocytes, Mononuclear; Male; MicroRNAs; Transcriptome; X-Rays
PubMed: 25017500
DOI: 10.1186/1755-8794-7-43 -
Radiation Research Jun 2016Telomeres consist of GC-rich DNA repeats and the "shelterin" protein complex that together protect chromosome ends from fusion and degradation. Telomeres shorten with...
Telomeres consist of GC-rich DNA repeats and the "shelterin" protein complex that together protect chromosome ends from fusion and degradation. Telomeres shorten with age due to incomplete end replication and upon exposure to environmental and intrinsic stressors. Exposure to ionizing radiation is known to modulate telomere length. However, the response of telomere length in humans chronically exposed to radiation is poorly understood. Here, we studied relative telomere length (RTL) by IQ-FISH to leukocyte nuclei in a group of 100 workers from the plutonium production facility at the Mayak Production Association (PA) who were chronically exposed to alpha-emitting ((239)Pu) radiation and/or gamma (photon) radiation, and 51 local residents serving as controls, with a similar mean age of about 80 years. We applied generalized linear statistical models adjusted for age at biosampling and the second exposure type on a linear scale and observed an age-dependent telomere length reduction. In those individuals with the lowest exposure, a significant reduction of about 20% RTL was observed, both for external gamma radiation (≤1 Gy) and internal alpha radiation (≤0.05-0.1 Gy to the red bone marrow). In highly exposed individuals (>0.1 Gy alpha, 1-1.5 Gy gamma), the RTL was similar to control. Stratification by gender revealed a significant (∼30%) telomere reduction in low-dose-exposed males, which was absent in females. While the gender differences in RTL may reflect different working conditions, lifestyle and/or telomere biology, absence of a dose response in the highly exposed individuals may reflect selection against cells with short telomeres or induction of telomere-protective effects. Our observations suggest that chronic systemic exposure to radiation leads to variable dose-dependent effects on telomere length.
Topics: Aged; Aged, 80 and over; Aging; Alpha Particles; Dose-Response Relationship, Radiation; Female; Gamma Rays; Humans; Male; Middle Aged; Nuclear Reactors; Occupational Exposure; Russia; Telomere; Time Factors
PubMed: 27340887
DOI: 10.1667/RR14271.1 -
Applied Radiation and Isotopes :... Sep 2022Although alpha-emitting radioisotopes have favorable characteristics for limiting external exposure to radiation workers, there are significant dose consequences...
Although alpha-emitting radioisotopes have favorable characteristics for limiting external exposure to radiation workers, there are significant dose consequences associated with accidental internal uptake. Consequently, regulatory requirements and license restrictions are designed to limit such risks to users. This paper will review regulatory limits for decommissioning financial assurance and annual limits on intake for actinium-227, review US Nuclear Regulatory Commission guidance for alpha contamination monitoring, and discuss regulatory examples from the Wisconsin Department of Health Services.
Topics: Actinium; Alpha Particles; Guidelines as Topic; Licensure; Occupational Health; Radiation Exposure; Social Control, Formal
PubMed: 35777201
DOI: 10.1016/j.apradiso.2022.110337 -
Microscopy Research and Technique May 2017
Topics: Alpha Particles; Erythrocyte Membrane; Erythrocytes
PubMed: 28146306
DOI: 10.1002/jemt.22844 -
Radioisotopes Mar 1990