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1.
J Radiol Prot ; 43(3)2023 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-37339608

RESUMEN

A monitoring programme, in place since 2006, continues to recover radioactive particles (<2 mm diameter) and larger objects from the beaches of West Cumbria. The potential risks to members of the public using the beaches are mainly related to prolonged skin contact with or the inadvertent ingestion of small particles. Most particles are classified as either 'beta-rich' or 'alpha-rich' and are detected as a result of their caesium-137 or americium-241 content. Beta-rich particles generally also contain strontium-90, with90Sr:137Cs ratios of up to about 1:1, but typically <0.1:1. Alpha-rich particles contain plutonium isotopes, with Pu:241Amαratios usually around 0.5-0.6:1. 'Beta-rich' particles have the greatest potential to cause localised skin damage if held in stationary contact with the skin for prolonged periods. However, it is concluded that only particles of >106Bq of137Cs, with high90Sr:137Cs ratios, would pose a significant risk of causing acute skin ulceration. No particles of this level of activity have been found. Inadvertent ingestion of a particle will result in the absorption to blood of a small proportion of the radionuclide content of the particle. The subsequent retention of radionuclides in body organs and tissues presents a potential risk of the development of cancer. For 'beta-rich' particles with typical activities (mean 2 × 104Bq137Cs, Sr:Cs ratio of 0.1:1), the estimated committed effective doses are about 30µSv for adults and about 40µSv for 1 year old infants, with lower values for 'alpha-rich' particles of typical activities. The corresponding estimates of lifetime cancer incidence following ingestion for both particle types are of the order of 10-6for adults and up to 10-5for infants. These estimates are subject to substantial uncertainties but provide an indication of the low risks to members of the public.


Asunto(s)
Playas , Exposición a Riesgos Ambientales , Residuos Radiactivos , Contaminantes Radiactivos del Suelo , Humanos , Lactante , Radioisótopos de Cesio/efectos adversos , Radioisótopos de Cesio/análisis , Plutonio/efectos adversos , Plutonio/análisis , Contaminantes Radiactivos del Suelo/efectos adversos , Contaminantes Radiactivos del Suelo/análisis , Reino Unido , Residuos Radiactivos/efectos adversos , Residuos Radiactivos/análisis , Adulto , Medición de Riesgo , Exposición a Riesgos Ambientales/efectos adversos , Monitoreo del Ambiente , Piel/efectos de la radiación , Ingestión de Alimentos , Neoplasias/inducido químicamente , Partículas beta/efectos adversos , Partículas alfa/efectos adversos
2.
PLoS One ; 16(10): e0257605, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34648511

RESUMEN

The objective of this study is to develop a skeleton model for assessing active marrow dose from bone-seeking beta-emitting radionuclides. This article explains the modeling methodology which accounts for individual variability of the macro- and microstructure of bone tissue. Bone sites with active hematopoiesis are assessed by dividing them into small segments described by simple geometric shapes. Spongiosa, which fills the segments, is modeled as an isotropic three-dimensional grid (framework) of rod-like trabeculae that "run through" the bone marrow. Randomized multiple framework deformations are simulated by changing the positions of the grid nodes and the thickness of the rods. Model grid parameters are selected in accordance with the parameters of spongiosa microstructures taken from the published papers. Stochastic modeling of radiation transport in heterogeneous media simulating the distribution of bone tissue and marrow in each of the segments is performed by Monte Carlo methods. Model output for the human femur at different ages is provided as an example. The uncertainty of dosimetric characteristics associated with individual variability of bone structure was evaluated. An advantage of this methodology for the calculation of doses absorbed in the marrow from bone-seeking radionuclides is that it does not require additional studies of autopsy material. The biokinetic model results will be used in the future to calculate individual doses to members of a cohort exposed to 89,90Sr from liquid radioactive waste discharged to the Techa River by the Mayak Production Association in 1949-1956. Further study of these unique cohorts provides an opportunity to gain more in-depth knowledge about the effects of chronic radiation on the hematopoietic system. In addition, the proposed model can be used to assess the doses to active marrow under any other scenarios of 90Sr and 89Sr intake to humans.


Asunto(s)
Partículas beta/efectos adversos , Médula Ósea/efectos de la radiación , Huesos/efectos de la radiación , Adolescente , Adulto , Anciano , Niño , Preescolar , Simulación por Computador , Femenino , Hematopoyesis/efectos de la radiación , Humanos , Lactante , Masculino , Persona de Mediana Edad , Modelos Biológicos , Método de Montecarlo , Dosis de Radiación , Radiometría , Procesos Estocásticos , Adulto Joven
3.
J Nucl Med ; 62(6): 795-801, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33127621

RESUMEN

Targeted therapies for multiple myeloma (MM) include the anti-CD38 antibody daratumumab, which, in addition to its inherent cytotoxicity, can be radiolabeled with tracers for imaging and with ß- and α-emitter radionuclides for radioimmunotherapy. Methods: We have compared the potential therapeutic efficacy of ß- versus α-emitter radioimmunotherapy using radiolabeled DOTA-daratumumab in a preclinical model of disseminated multiple myeloma. Multiple dose levels were investigated to find the dose with the highest efficacy and lowest toxicity. Results: In a dose­response study with the ß-emitter 177Lu-DOTA-daratumumab, the lowest tested dose, 1.85 MBq, extended survival from 37 to 47 d but did not delay tumor growth. Doses of 3.7 and 7.4 MBq extended survival to 55 and 58 d, respectively, causing a small equivalent delay in tumor growth, followed by regrowth. The higher dose, 11.1 MBq, eradicated the tumor but had no effect on survival compared with untreated controls, because of whole-body toxicity. In contrast, the α-emitter 225Ac-DOTA-daratumumab had a dose-dependent effect, in which 0.925, 1.85, and 3.7 kBq increased survival, compared with untreated controls (35 d), to 47, 52, and 73 d, respectively, with a significant delay in tumor growth for all 3 doses. Higher doses of 11.1 and 22.2 kBq resulted in equivalent survival to 82 d but with significant whole-body toxicity. Parallel studies with untargeted 225Ac-DOTA-trastuzumab conferred no improvement over untreated controls and resulted in whole-body toxicity. Conclusion: We conclude, and mathematic modeling confirms, that maximal biologic doses were achieved by targeted α-therapy and demonstrated 225Ac to be superior to 177Lu in delaying tumor growth and decreasing whole-body toxicity.


Asunto(s)
ADP-Ribosil Ciclasa 1/inmunología , Partículas beta/uso terapéutico , Mieloma Múltiple/patología , Mieloma Múltiple/radioterapia , Radioinmunoterapia , Animales , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Partículas beta/efectos adversos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Humanos , Terapia Molecular Dirigida , Mieloma Múltiple/inmunología , Seguridad
4.
Int J Radiat Oncol Biol Phys ; 108(3): 770-778, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32473181

RESUMEN

BACKGROUND: Radon and its progenies contribute significantly to the natural background radiation and cause several thousands of lung cancer cases per year worldwide. Moreover, patients with chronic inflammatory joint diseases are treated in radon galleries. Due to the complex nature of radon exposure, the doses associated with radon exposures are difficult to assess. Hence, there is a clear need to directly measure dose depositions from radon exposures to provide reliable risk estimates for radiation protection guidelines. OBJECTIVES: We aimed to assess tissue-specific radiation doses associated with radon activity concentrations, that deposit similar dose levels as the annual natural radon exposure or radon gallery visits. METHODS: We exposed mice to defined radon concentrations, quantified the number of 53BP1 foci as a measure of induced DNA damage, and compared it with the number of foci induced by known doses of reference-type radiations. An image-based analysis of the 3-dimensional foci pattern provided information about the radiation type inflicting the DNA damage. RESULTS: A 1-hour exposure to 440 kBq/m3 radon-induced DNA damage corresponding to a dose of ∼10 mGy in the lung and ∼3.3 mGy in the kidney, heart, and liver. A 1-hour exposure to 44 kBq/m3 provided values consistent with a linear relationship between dose and radon concentration. Two-thirds of the dose in the lung was caused by α-particles. The dose in the kidney, heart, and liver and one-third of the dose in the lung likely resulted from ß- and γ-rays. DISCUSSION: We found that radon exposures mainly lead to α-particle-induced DNA damage in the lung, consistent with the lung cancer risk obtained in epidemiologic studies. Our presented biodosimetric approach can be used to benchmark risk model calculations for radiation protection guidelines and can help to understand the therapeutic success of radon gallery treatments.


Asunto(s)
Daño del ADN , Neoplasias Pulmonares/etiología , Neoplasias Inducidas por Radiación/etiología , Dosis de Radiación , Exposición a la Radiación/análisis , Radón/efectos adversos , Partículas alfa/efectos adversos , Animales , Partículas beta/efectos adversos , Relación Dosis-Respuesta en la Radiación , Rayos gamma/efectos adversos , Corazón/efectos de la radiación , Histonas/análisis , Riñón/efectos de la radiación , Hígado/efectos de la radiación , Pulmón/efectos de la radiación , Ratones , Ratones Endogámicos C57BL , Exposición a la Radiación/efectos adversos , Factores de Tiempo , Proteína 1 de Unión al Supresor Tumoral P53/análisis
5.
Int J Radiat Biol ; 96(8): 972-979, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32394793

RESUMEN

Background: The value of relative biological effectiveness of tritium increases at low dose domain, which results in the suspicion of weighting factor of 1 for tritium after low dose exposure. Thus, present study was carried out to analyze the differences in the cellular responses at early and late period between low dose of tritium ß-rays and γ-rays radiation.Methods: MCF-10A cells were exposed to low dose of tritium ß-rays or γ-rays, then cellular behaviors, such as DNA double strand breaks (DSBs), apoptosis, reactive oxygen species (ROS) level and inflammatory relevant gene expression were analyzed at early and late period post-irradiation.Results: At early period the elimination of DSB foci produced by HTO is longer than γ-rays. High ROS level and a continual change of cell cycle distribution are observed in HTO radiation group. Based on the results of RNA sequencing, Ingenuity Pathway Analysis (IPA) indicates TNFR1 signaling and production of nitric oxide and ROS are activated as an acute response at 24 h post radiation. Moreover, it also shows a disturbance in cholesterol biosynthesis. The results of 30 days point that there is a lasting active inflammatory response, accompanying with a persistent high expression of relevant cytokines, such as TNF and IL1R.Conclusion: Compared to an acute response induced by γ-rays, a persistent inflammatory response exists in HTO-irradiated cells when cultured for 30 days, which might be related to accumulation of tritium in the form of organically bound tritium (OBT) in cellular DNA or lipids.


Asunto(s)
Partículas beta/efectos adversos , Tritio/efectos adversos , Línea Celular Tumoral , Relación Dosis-Respuesta en la Radiación , Rayos gamma/efectos adversos , Regulación de la Expresión Génica/efectos de la radiación , Humanos , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología
6.
Sci Rep ; 10(1): 4299, 2020 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-32152426

RESUMEN

This paper presents information on the gross alpha and gross beta activity concentrations of two hundred twenty-six groundwater samples collected by gas flow proportional counters in southern Vietnam. The gross alpha results in the water samples ranged from 0.024 to 0.748 Bq L-1 with a mean of 0.183 ± 0.034 Bq L-1, and the gross beta results in the water samples ranged from 0.027-0.632 Bq L-1 with a mean of 0.152 ± 0.015 Bq L-1. The values obtained in this work were compared with those previously published for various regions or countries. Next, untreated and treated groundwater samples were analyzed to assess their influences on the treatment process. The results showed that there were differences in the minimum detection concentrations and the mean activity values between the untreated and treated groundwater samples (The p-value of the mean comparison tests is significant with p < 0.05). In both sample groups, there was a strong positive correlation of the gross alpha versus the gross beta results (r > 0.6). This means that among the radionuclides, the major sources of beta radiation are uranium and thorium decay series radionuclides. Finally, the annual effective dose for adults (>17 years) was calculated based on the assumption that major radionuclides have the highest effective dose conversion factors. In general, the results for Pb-210, Ra-226, and Ra-228 were observed to be lower than the recommended reference values established by the World Health Organization and the International Atomic Energy Agency, except for the value of Po-210.


Asunto(s)
Partículas alfa/efectos adversos , Partículas beta/efectos adversos , Agua Subterránea/análisis , Salud Pública , Exposición a la Radiación/prevención & control , Monitoreo de Radiación/métodos , Contaminantes Radiactivos del Agua/análisis , Agua Potable/análisis , Promoción de la Salud , Humanos , Dosis de Radiación , Contaminantes Radiactivos del Agua/normas
7.
Sci Rep ; 9(1): 10365, 2019 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-31316118

RESUMEN

Insoluble radioactive microparticles emitted by the incident at the Fukushima nuclear power plant have drawn keen interests from the viewpoint of radiation protection. Cs-bearing particles have been assumed to adhere in the long term to trachea after aspirated into respiratory system, leading to heterogeneous dose distribution within healthy tissue around the particles. However, the biological effects posed by an insoluble radioactive particle remain unclear. Here, we show cumulative DNA damage in normal human lung cells proximal and distal to the particle (ß-ray and γ-ray-dominant areas, respectively) under localized chronic exposure in comparison with uniform exposure. We put a Cs-bearing particle into a microcapillary tip and placed it onto a glass-base dish containing fibroblast or epithelial cells cultured in vitro. A Monte Carlo simulation with PHITS code provides the radial distribution of absorbed dose-rate around the particle, and subsequently we observed a significant change in nuclear γ-H2AX foci after 24 h or 48 h exposure to the particle. The nuclear foci in the cells distal to the particle increased even under low-dose-rate exposure compared with uniform exposure to 137Cs γ-rays, which was suppressed by a treatment with a scavenger of reactive oxygen species. In contrast, such focus formation was less manifested in the exposed cells proximal to the particle compared with uniform exposure. These data suggest that the localized exposure to a Cs-bearing particle leads to not only disadvantage to distal cells but also advantage to proximal cells. This study is the first to provide quantitative evaluation for the spatial distribution of DNA double strand breaks after the heterogeneous chronic exposure to a Cs-bearing particle in comparison with uniform Cs exposure.


Asunto(s)
Radioisótopos de Cesio/toxicidad , Roturas del ADN de Doble Cadena , Daño del ADN , ADN/efectos de la radiación , Células Epiteliales/efectos de la radiación , Fibroblastos/efectos de la radiación , Partículas beta/efectos adversos , Bronquios/citología , Línea Celular , Línea Celular Transformada , Relación Dosis-Respuesta en la Radiación , Células Epiteliales/química , Fibroblastos/química , Depuradores de Radicales Libres , Accidente Nuclear de Fukushima , Rayos gamma/efectos adversos , Regulación de la Expresión Génica/efectos de la radiación , Histonas/biosíntesis , Histonas/genética , Humanos , Pulmón/citología , Tamaño de la Partícula , Especies Reactivas de Oxígeno , Solubilidad
8.
Toxicol In Vitro ; 61: 104608, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31348984

RESUMEN

Tritium is an important radioactive waste which needs to be monitored for radiation protection. Due to long biological half-life of organically bound tritium (OBT), the adverse consequence caused by chronic exposure of tritiated water (HTO) attracts concern. In this study, fibroblast cells were exposed to 2 × 106 Bq/ml HTO to investigate the cellular behaviors. The dose relationship of survival fraction and γH2AX foci was a "U-shaped" curve. And the results of γH2AX intensity produced by ICCM, which was obtained from different doses, demonstrated bystander signal accounted for the protective effects induced by intermediate dose of 100 mGy. The comparison of temporal kinetics and spatial dynamics of DNA repair between tritium ß-rays and γ-rays showed longer time was need for the dephosphorylation of H2AX protein after HTO exposure. It indicated complex cluster DSBs induced by tritium ß-rays at the low dose impaired efficient recovery of DNA damage, which bear responsibility for the persistence of residual foci after low dose expsoure. It suggests after exposed to low dose radiation cells prefer to eliminate damage population to avoid DNA damage increasing the mutation potential.


Asunto(s)
Partículas beta/efectos adversos , Daño del ADN , Células Epiteliales/efectos de la radiación , Rayos gamma/efectos adversos , Mutágenos/toxicidad , Tritio/toxicidad , Mama/citología , Línea Celular , Células Epiteliales/metabolismo , Histonas/metabolismo , Humanos , Agua
9.
Radiat Res ; 192(2): 145-158, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31166846

RESUMEN

While cutaneous radiation injury (CRI) is generally referenced as a consequence of a nuclear attack, it can also be caused by less dangerous events such as the use of dirty bombs, industrial radiological accidents, or accidental overexposure of beta (ß) particle or gamma (γ) radiation sources in medical procedures. Although the gross clinical consequences of these injuries have been well documented, relatively little is known about the molecular changes underlying the progression of pathology. Here we describe a porcine model of cutaneous radiation injury after skin was exposed to strontium-90 b particle at doses of 16-42 Gy and characterize the anatomical and molecular changes over 70 days. The results show that irradiated sites displayed dosedependent increases in erythema and moist desquamation that peaked between days 35 and 42. Dose-dependent histopathological changes were observed, with higher doses exhibiting increased inflammation and epidermal hyperplasia beyond day 35. Furthermore, immunohistochemistry showed that exposure to 37 Gy ß-particle radiation decreased epidermal cell proliferation and desmosomal junction proteins at day 70, suggesting compromised epidermal integrity. Metabolomic analysis of biopsies revealed dose- and time-dependent changes as high as 252-fold in several metabolites not previously linked to CRI. These alterations were seen in pathways reflecting protein degradation, oxidative stress, eicosanoid production, collagen matrix remodeling, mitochondrial stress, cell membrane composition and vascular disruption. Taken together, these data show that exposure to high doses of ß particle damaged the molecular processes underlying skin integrity to a greater extent and for a longer period of time than has been shown previously. These findings further understanding of radiation-induced skin injury and serve as a foundation for the development and testing of potential therapeutics to treat CRI.


Asunto(s)
Partículas beta/efectos adversos , Piel/lesiones , Piel/efectos de la radiación , Animales , Proliferación Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Femenino , Piel/metabolismo , Piel/patología , Porcinos , Transcriptoma/efectos de la radiación
10.
Biomed Phys Eng Express ; 6(1): 015007, 2019 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-33438595

RESUMEN

PURPOSE: Radiation skin injuries are difficult to quantitatively assess. Various scoring scales exist based on visual images and can be used in quantitative form for histological scoring. As an alternative to human scoring systems, an automated, quantitative system is proposed to provide unbiased scoring of radiation skin injury biopsy samples, with comparisons to human-based scoring systems. MATERIALS AND METHODS: A unique algorithm was developed and tested on a sample pool obtained from in-vivo beta radiation experiments with a porcine model. The grading results achieved by the developed algorithm and those provided by an expert histopathologist are compared. RESULTS: The extent of the epidermal necrosis is quantified in terms of the number of dead cells and their respective distribution across the length of the samples. The accuracy of the grading performed by the automated algorithm is comparable to that of a trained histopathologist, as demonstrated by statistically significant difference between the grades. CONCLUSIONS: This study demonstrates the feasibility of the proposed method as a potential tool designed to aid in the histopathological analysis of the tissues affected by beta radiation exposure. An expanded study with a larger sample pool is recommended to further improve the accuracy of the proposed algorithm.


Asunto(s)
Partículas beta/efectos adversos , Traumatismos Experimentales por Radiación/patología , Piel/patología , Piel/efectos de la radiación , Algoritmos , Animales , Automatización , Estudios de Factibilidad , Femenino , Necrosis , Patólogos , Porcinos
11.
Int J Radiat Biol ; 94(11): 955-966, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30257126

RESUMEN

PURPOSE: Dose and dose rate are both appropriate for estimating risk from internally deposited radioactive materials. We investigated the role of dose rate on lung cancer induction in Beagle dogs following a single inhalation of strontium-90 (90Sr), cerium-144 (144Ce), yttrium-91 (91Y), or yttrium-90 (90Y). As retention of the radionuclide is dependent on biological clearance and physical half-life a representative quantity to describe this complex changing dose rate is needed. MATERIALS AND METHODS: Data were obtained from Beagle dog experiments from the Inhalation Toxicology Research Institute. The authors selected the dose rate at the effective half-life of each radionuclide (DRef). RESULTS: Dogs exposed to DRef (1-100 Gy/day) died within the first year after exposure from acute lung disease. Dogs exposed at lower DRef (0.1-10 Gy/day) died of lung cancer. As DRef decreased further (<0.1 Gy/day 90Sr, <0.5 Gy/day 144Ce, <0.9 Gy/day 91Y, <8 Gy/day 90Y), survival and lung cancer frequency were not significantly different from control dogs. CONCLUSION: Radiation exposures resulting from inhalation of beta-gamma emitting radionuclides that decay at different rates based on their effective half-life, leading to different rates of decrease in dose rate and cumulative dose, is less effective in causing cancer than acute low linear energy transfer exposures of the lung.


Asunto(s)
Partículas beta/efectos adversos , Rayos gamma/efectos adversos , Neoplasias Pulmonares/etiología , Neoplasias Inducidas por Radiación/etiología , Dosis de Radiación , Administración por Inhalación , Animales , Perros , Semivida , Medición de Riesgo
12.
PLoS One ; 13(7): e0197911, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30001320

RESUMEN

High-throughput gene expression analysis is increasingly used in radiation research for discovery of damage-related or absorbed dose-dependent biomarkers. In tissue samples, cell type-specific responses can be masked in expression data due to mixed cell populations which can preclude biomarker discovery. In this study, we deconvolved microarray data from thyroid tissue in order to assess possible bias from mixed cell type data. Transcript expression data [GSE66303] from mouse thyroid that received 5.9 Gy from 131I over 24 h (or 0 Gy from mock treatment) were deconvolved by cell frequency of follicular cells and C-cells using csSAM and R and processed with Nexus Expression. Literature-based signature genes were used to assess the relative impact from ionizing radiation (IR) or thyroid hormones (TH). Regulation of cellular functions was inferred by enriched biological processes according to Gene Ontology terms. We found that deconvolution increased the detection rate of significantly regulated transcripts including the biomarker candidate family of kallikrein transcripts. Detection of IR-associated and TH-responding signature genes was also increased in deconvolved data, while the dominating trend of TH-responding genes was reproduced. Importantly, responses in biological processes for DNA integrity, gene expression integrity, and cellular stress were not detected in convoluted data-which was in disagreement with expected dose-response relationships-but upon deconvolution in follicular cells and C-cells. In conclusion, previously reported trends of 131I-induced transcriptional responses in thyroid were reproduced with deconvolved data and usually with a higher detection rate. Deconvolution also resolved an issue with detecting damage and stress responses in enriched data, and may reduce false negatives in other contexts as well. These findings indicate that deconvolution can optimize microarray data analysis of heterogeneous sample material for biomarker screening or other clinical applications.


Asunto(s)
Células Neuroendocrinas/efectos de la radiación , ARN Mensajero/genética , Células Epiteliales Tiroideas/efectos de la radiación , Glándula Tiroides/efectos de la radiación , Análisis de Matrices Tisulares/métodos , Transcriptoma , Animales , Partículas beta/efectos adversos , Femenino , Rayos gamma/efectos adversos , Regulación de la Expresión Génica , Ontología de Genes , Radioisótopos de Yodo , Ratones , Ratones Desnudos , Anotación de Secuencia Molecular , Células Neuroendocrinas/citología , Células Neuroendocrinas/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/metabolismo , Células Epiteliales Tiroideas/citología , Células Epiteliales Tiroideas/metabolismo , Glándula Tiroides/citología , Glándula Tiroides/metabolismo , Hormonas Tiroideas/metabolismo , Hormonas Tiroideas/farmacología
13.
Health Phys ; 115(2): 281-294, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29957689

RESUMEN

Retrospective dose assessment following acute radiation exposures during radiological incidents can be difficult and inaccurate due to the large uncertainties associated with dose estimation. However, rapid and accurate dose assessment is critical following an incident so that appropriate treatment can be provided to the patient as early as possible. Incident dose assessment relies heavily on biological dosimetry with corresponding large uncertainties for inhomogeneous exposures, resulting from the estimates of whole-body doses, while the assessment of absorbed doses to individual tissues might actually be more appropriate for acute radiation exposures. Incident exposure scenarios for orphan sources placed in a breast or back pants pocket were modeled using the International Commission on Radiological Protection computational reference male and female and the Monte Carlo N-particle code MCNP6 to compute absorbed dose conversion coefficients for organs of interest for monoenergetic photon and beta sources. The absorbed dose conversion coefficients are intended for use in conjunction with source information to rapidly estimate absorbed doses to organs of interest from radiological sources in one of the two pocket geometries. Absorbed dose conversion coefficients also have been calculated specifically for Co, Cs, and Ir. Those absorbed dose conversion coefficients were applied to data from a radiological incident in Yanango, Peru, for comparison with published dose assessments; the results agree within 20%. The conversion coefficients are expected to provide an accurate tool for assessing doses for the modeled geometries, provided uncertainties due to the exact source-body geometry and exposure time are considered.


Asunto(s)
Partículas beta/efectos adversos , Rayos gamma/efectos adversos , Fantasmas de Imagen , Ropa de Protección/normas , Exposición a la Radiación/análisis , Protección Radiológica/métodos , Irradiación Corporal Total/efectos adversos , Femenino , Humanos , Masculino , Dosis de Radiación , Radiometría , Estudios Retrospectivos
14.
Radiat Res ; 190(3): 236-247, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29944461

RESUMEN

The use of targeted radionuclide therapy for cancer is on the rise. While beta-particle-emitting radionuclides have been extensively explored for targeted radionuclide therapy, alpha-particle-emitting radionuclides are emerging as effective alternatives. In this context, fundamental understanding of the interactions and dosimetry of these emitted particles with cells in the tumor microenvironment is critical to ascertaining the potential of alpha-particle-emitting radionuclides. One important parameter that can be used to assess these metrics is the S-value. In this study, we characterized several alpha-particle-emitting radionuclides (and their associated radionuclide progeny) regarding S-values in the cellular and tumor-metastasis environments. The Particle and Heavy Ion Transport code System (PHITS) was used to obtain S-values via Monte Carlo simulation for cell and tumor metastasis resulting from interactions with the alpha-particle-emitting radionuclides, lead-212 (212Pb), actinium-225 (225Ac) and bismuth-213 (213Bi); these values were compared to the beta-particle-emitting radionuclides yttrium-90 (90Y) and lutetium-177 (177Lu) and an Auger-electron-emitting radionuclide indium-111 (111In). The effect of cellular internalization on S-value was explored at increasing degree of internalization for each radionuclide. This aspect of S-value determination was further explored in a cell line-specific fashion for six different cancer cell lines based on the cell dimensions obtained by confocal microscopy. S-values from PHITS were in good agreement with MIRDcell S-values (cellular S-values) and the values found by Hindié et al. (tumor S-values). In the cellular model, 212Pb and 213Bi decay series produced S-values that were 50- to 120-fold higher than 177Lu, while 225Ac decay series analysis suggested S-values that were 240- to 520-fold higher than 177Lu. S-values arising with 100% cellular internalization were two- to sixfold higher for the nucleus when compared to 0% internalization. The tumor dosimetry model defines the relative merit of radionuclides and suggests alpha particles may be effective for large tumors as well as small tumor metastases. These results from PHITS modeling substantiate emerging evidence that alpha-particle-emitting radionuclides may be an effective alternative to beta-particle-emitting radionuclides for targeted radionuclide therapy due to preferred dose-deposition profiles in the cellular and tumor metastasis context. These results further suggest that internalization of alpha-particle-emitting radionuclides via radiolabeled ligands may increase the relative biological effectiveness of radiotherapeutics.


Asunto(s)
Partículas alfa/uso terapéutico , Partículas beta/uso terapéutico , Neoplasias/radioterapia , Actinio/uso terapéutico , Partículas alfa/efectos adversos , Partículas beta/efectos adversos , Bismuto/uso terapéutico , Relación Dosis-Respuesta en la Radiación , Humanos , Radioisótopos de Plomo/uso terapéutico , Lutecio/uso terapéutico , Metástasis de la Neoplasia , Neoplasias/patología , Radioisótopos/uso terapéutico , Radioisótopos de Itrio/uso terapéutico
15.
J Am Heart Assoc ; 7(6)2018 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-29545261

RESUMEN

BACKGROUND: The cardiovascular effects of low-level environmental radiation exposures are poorly understood. Although particulate matter (PM) has been linked to cardiovascular morbidity and mortality, and elevated blood pressure (BP), the properties promoting its toxicity remain uncertain. Addressing a knowledge gap, we evaluated whether BP increased with higher exposures to radioactive components of ambient PM, herein referred to as particle radioactivity (PR). METHODS AND RESULTS: We performed a repeated-measures analysis of 852 men to examine associations between PR exposure and BP using mixed-effects regression models. As a surrogate for PR, we used gross ß activity, measured by the US Environmental Protection Agency's radiation monitoring network. Higher PR exposure was associated with increases in both diastolic BP and systolic BP, for exposures from 1 to 28 days. An interquartile range increase in 28-day PR exposure was associated with a 2.95-mm Hg increase in diastolic BP (95% confidence interval, 2.25-3.66; P<0.001) and a 3.94-mm Hg increase in systolic BP (95% confidence interval, 2.62-5.27; P<0.001). For models including both PR and PM ≤2.5 µm, the PR-BP associations remained stable and significant. For models including PR and black carbon or PR and particle number, the PR-BP associations were attenuated; however, they remained significant for many exposure durations. CONCLUSIONS: This is the first study to demonstrate the potential adverse effects of PR on both systolic and diastolic BPs. These were independent and similar in magnitude to those of PM ≤2.5 µm, black carbon, and particle number. Understanding the effects of particle-bound radionuclide exposures on BP may have important implications for environmental and public health policy.


Asunto(s)
Partículas beta/efectos adversos , Presión Sanguínea/efectos de la radiación , Material Particulado/efectos adversos , Exposición a la Radiación/efectos adversos , Factores de Edad , Anciano , Envejecimiento , Monitoreo del Ambiente/métodos , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Monitoreo de Radiación , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Factores de Tiempo
16.
Nucl Med Rev Cent East Eur ; 21(1): 26-31, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29319135

RESUMEN

BACKGROUND: There is a clinical need for therapeutic alternative in patients with persisting painful arthritis of AC-joint and failure of previous treatments. However, no radiopharmaceutical is currently explicitly approved for radiosynoviorthesis of acromioclavicular joint. The aim of our study was to prospectively assess the efficacy and safety of radiosynoviorthesis of acromioclavicular joint using erbium-169 citrate. MATERIAL AND METHODS: Radiosynoviorthesis of acromioclavicular joint was performed in 51 consecutive patients (18 males, 33 females) mean age 64.3 (range 43.8-82.6, median 63.6) years with clinically confirmed arthritis of 85 acromioclavicular joints. The efficacy of RSO was reported by patients according to 10-step visual analogue scale of pain (VAS) (0 = no pain, 10 = most severe pain) at 6 months after radiosynoviorthesis and by ranking the global therapeutic effect of RSO in 4 categories (1 = the best effect, 4 = no change). To assess the variation of blood perfusion in treated joints, the efficacy of RSO was also evaluated by variation of target (acromioclavicular joint)/non-target (soft tissue) uptake ratio (T/NTR) of metylendiphosphonate (99mTc) measured as number of counts over region of interest on blood pool phase of two-phase bone scintigraphy performed before and 6 months after RSO. RESULTS: Radiosynoviorthesis was followed by significant decrease in VAS, mean - 3.1 (-47%). Excellent, good, moderate and bad response was observed in 57 (67%), 25 (29%), 1 (1%) and in 2 (2%) of acromioclavicular joints respectively. A significant correlation between decrease of T/NTR and variation of VAS in % (ρ = 0.532, p < 0.0001) and between T/NTR and subjective evaluation of therapeutic effect in scale 1-4 (ρ = 0.388, p = 0.0002) was observed. However, it was not possible to identify the cut-off value of relative decrease in T/NTR showing sufficient sensitivity and specificity to detect the therapeutic response. CONCLUSION: Results of this prospective study permit to conclude a good efficacy and safety of radiosynoviorthesis using erbium-169 citrate in a series of patients with arthritis of acromioclavicular joint in whom previous line(s) of treatment did not lead to satisfactory pain relief.


Asunto(s)
Articulación Acromioclavicular/efectos de la radiación , Artritis Reumatoide/radioterapia , Ácido Cítrico/uso terapéutico , Erbio/uso terapéutico , Radioisótopos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Partículas beta/efectos adversos , Partículas beta/uso terapéutico , Erbio/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radioisótopos/efectos adversos , Seguridad
17.
Georgian Med News ; (263): 93-99, 2017 Feb.
Artículo en Ruso | MEDLINE | ID: mdl-28452734

RESUMEN

The aim of our study was to study influence of ionizing radiation on the locomotor activity and body weight of rats, for this animals was irradiated by via inhalation. Beta- emitter 56Mn was obtained by neutron activation of powdered MnО2 by using nuclear reactor IVG.1M (experimental facility «Baikal-1¼, Kurchatov, Kazakhstan). Exposure of rats to radioactive powder had two way, the first experiment was contained only air filter for animal's breathing and the second with the system of forced ventilation. Also we developed the method for observation of the locomotor activity of rats, based on quantitative data. The experiment was conducted on 8 «Wistar¼ breed white laboratory rats. Statistical analysis was performed using descriptive statistics and non-parametric test. Based on our data, we can say that our method has the advantage over the others is that there is no need to move about the animal out of the box in the test field. So we reduce animal stress factor, as the transfer of an animal from one to second place creates additional stress for him. The initial activity of the pulverized powder in both experiments were 2,74х108Bq, but in the second experiment when we used the system of forced ventilation, internal radiation doses were 0.041±0.0075 Gy, this didn't have effect on locomotor activity of rats (Z= -0,841, р=0,4). In the first experiment where we used only air filter for animal's breathing internal radiation doses were 0.15±0.025 Gr, that showed a decrease in locomotor activity in rats (Z=-6,653, р=0,001). After exposure to ionizing radiation changes in the mammals' weight were not found. Thus, based on our data we have made conclusion, that even after a single irradiation at low dose 0.15±0.025 Gr changes occur in the nervous system.


Asunto(s)
Peso Corporal/efectos de la radiación , Compuestos de Manganeso , Actividad Motora/efectos de la radiación , Óxidos , Administración por Inhalación , Animales , Partículas beta/efectos adversos , Manganeso , Polvos , Radioisótopos , Ratas Wistar
18.
Radiat Prot Dosimetry ; 176(3): 211-216, 2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-28115659

RESUMEN

106Ru/106Rh is unique amongst other commonly used beta sources such as 147Pm, 85Kr, 204Tl, 32P, natU and 90Sr/90Y in the sense that it is capable of simultaneously delivering shallow/skin, eye lens and deep/whole body doses (WBDs) and they differ from each other substantially. In view of this, the investigation of various quantities defined for individual monitoring is possible and this makes 106Ru/106Rh beta source, a classical example in radiation protection and dosimetry. This led us to estimate skin, eye lens and WBDs for 106Ru/106Rh beta source. Optically stimulated luminescence based ultra-thin α-Al2O3:C disc dosimeters were used in the present study. Typical values (relative) of the eye lens and whole body/deep doses with respective to the skin dose (100%) were experimentally measured as ~66 ± 4.6% and 17 ± 3.9%, respectively. The study shows that 106Ru/106Rh beta source is capable of delivering even WBD which is not the case with other beta sources.


Asunto(s)
Partículas beta/efectos adversos , Cristalino/efectos de la radiación , Radioisótopos/efectos adversos , Radiometría/métodos , Rodio/efectos adversos , Rutenio/efectos adversos , Humanos , Modelos Anatómicos , Órganos en Riesgo/efectos de la radiación
19.
Radiats Biol Radioecol ; 57(1): 98-107, 2017 Jan.
Artículo en Inglés, Ruso | MEDLINE | ID: mdl-30698937

RESUMEN

At present volumetric activity of ß-emitting radionuclides in water at various locations of the Techa River ranges from 5 to 40-Bq/L; a specific activity of ß-emitting radionuclides in the bottom sediments at various locations ranges 10 Ito 106 Bq/kg dry weight. A significant increase of the erythroblast content in blood as compared to that in the roach from the reference watercourse (the Miass River) was observed during spawning in the spring. Due to this fact the number of erythrocytes was equal to that in the control animals under chronic radiation exposure at the dose rates of 0.9 and 16 µGy/day, and was insufficient at the dose rate of 108 gGy/day. During summer feeding no changes in the indexes of erythropoiesis in roach were observed under chronic radiation exposure at the dose rate of 0.9 µGy/day; the number of erythrocytes in the peripheral blood declines when the dose rates are 16 and 108 µGy/day. When performing a regression analysis, we revealed a dose-rate-dependent decrease in the absolute number of erythrocytes, normocytes, polychromatocytes, dividing and non-dividing erythroid cells in the peripheral blood of roach from the Techa River and an increase of a relative number of normochromatophylic erythrocytes.


Asunto(s)
Partículas beta/efectos adversos , Cyprinidae/sangre , Eritropoyesis/efectos de la radiación , Contaminantes Radiactivos del Agua/efectos adversos , Animales , Eritrocitos/patología , Eritrocitos/efectos de la radiación , Sedimentos Geológicos , Radioisótopos/efectos adversos , Estaciones del Año
20.
Mutat Res ; 791-792: 49-60, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27648955

RESUMEN

A single exposure to ionizing radiation (IR) results in an elevated cell-free DNA (cfDNA) content in the blood plasma. In this case, the cfDNA concentration can be a marker of the cell death in the organism. However, a chronic exposure to a low-dose IR enhances both the endonuclease activity and titer of antibodies to DNA in blood plasma, resulting in a decrease of the total concentration of circulating cfDNA in exposed people. In this case, the total cfDNA concentration should not be considered as a marker of the cell death in an exposed body. We assumed that a pool of the cfDNA circulating in the exposed people contains DNA fragments, which are resistant to a double-strand break formation in the environment of the elevated plasma endonuclease activity, and can be accumulated in the blood plasma. In order to test this hypothesis, we studied the content of GC-rich sequences (69%GC) of the transcribed region of human ribosomal repeat (rDNA), as well as the content of AT-rich repeat (63%AT) of satellite III (1q12) in the cfDNA samples obtained from 285 individuals. We have found that a chronic exposure to gamma-neutron radiation (N=88) and tritium ß-radiation (N=88) evokes an increase of the rDNA content (RrDNA index) and a decrease of the satellite III content (RsatIII index) in the circulating cfDNA as compared with the cfDNA of non-exposed people (N=109). Such index that simultaneously displays both the increase of rDNA content and decrease of satellite III content in the cfDNA (RrDNA/RsatIII) can be recommended as a marker of chronic processes in the body that involve the elevated cell death rate and/or increased blood plasma endonuclease activity.


Asunto(s)
Partículas beta/efectos adversos , ADN Ribosómico/sangre , ADN Satélite/sangre , Rayos gamma/efectos adversos , Exposición Profesional/efectos adversos , Exposición a la Radiación/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Roturas del ADN de Doble Cadena , ADN Ribosómico/genética , ADN Satélite/genética , Relación Dosis-Respuesta en la Radiación , Secuencia Rica en GC , Humanos , Persona de Mediana Edad , Neutrones , Exposición Profesional/análisis , Dosis de Radiación , Exposición a la Radiación/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Federación de Rusia , Secuencias Repetidas en Tándem/genética , Tritio , Adulto Joven
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