The JC-1 dye is widely used in apoptosis studies to monitor mitochondrial health. The probe was tested in vitro on two established cell lines and peripheral porcine blood lymphocytes after gamma irradiation (IR) to assess its potential in biodosimetric evaluation. In brief, we stained irradiated and non-irradiated cells with the JC-1 dye to determine the existing changes in mitochondrial membrane potential and monitor cell health through flow cytometry. The stage of injury in these cells was evaluated through an irradiated versus non-irradiated ratio (IVNIR), comparing the relative proportion of polarised cells containing red JC-1 aggregates. We observed a decreasing IVNIR as the radiation dose increased (i.e. 0.5; 1; 2; 4; 6; 8 and 10 Gy), performing the analysis at 4, 8 and 24 h after IR in all the tested cells. The results from the JC1-dye test showed that CD4 T lymphocytes were more sensitive to irradiation than other subpopulations.
This study establishes a new experimental approach for retrospective biodosimetric assessment by apoptosis detection ex vivo. For this purpose, we used mononuclear blood leukocytes isolated from the peripheral blood of irradiated Wistar rats and cultured them ex vivo for posterior analysis. Using flow cytometry, we distinguished apoptotic lymphocyte subsets individual biodosimetric potential at different time periods after exposure: B-lymphocytes 6-8 h (0-7 Gy), natural killer cells 24 h (0-7 Gy) and T-lymphocytes 24 h (0-1 Gy). This novel experimental design innovates through the need of a single blood sample from irradiated individuals for a complete biodosimetric assessment.
The dramatic rise in diagnostic procedures, radioisotope-based scans and intervention procedures has created a very valid concern regarding the long-term biological consequences from exposure to low doses of ionizing radiation. Despite its unambiguous medical benefits, additional knowledge on the health outcome of its use is essential. This review summarizes the available information regarding the biological consequences of low-dose radiation (LDR) exposure in humans (e.g. cytogenetic changes, cancer risk and radiation-induced cataracts. However, LDR studies remain relatively new and thus an encompassing view of its biological effects and relevant mechanisms in the human body is still needed.
- MeSH
- dávka záření MeSH
- ionizující záření * MeSH
- lidé MeSH
- počítačová rentgenová tomografie metody MeSH
- radiační poranění * etiologie prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Purpose: Insulin-like growth factor-1 (IGF-1) stimulates epithelial regeneration but may also induce life-threatening hypoglycemia. In our study, we first assessed its safety. Subsequently, we examined the effect of IGF-1 administered in different dose regimens on gastrointestinal damage induced by high doses of gamma radiation. Material and methods: First, fasting C57BL/6 mice were injected subcutaneously with IGF-1 at a single dose of 0, 0.2, 1, and 2 mg/kg to determine the maximum tolerated dose (MTD). The glycemic effect of MTD (1 mg/kg) was additionally tested in non-fasting animals. Subsequently, a survival experiment was performed. Animals were irradiated (60Co; 14, 14.5, or 15 Gy; shielded head), and IGF-1 was administered subcutaneously at 1 mg/kg 1, 24, and 48 h after irradiation. Simultaneously, mice were irradiated (60Co; 12, 14, or 15 Gy; shielded head), and IGF-1 was administered subcutaneously under the same regimen. Jejunum and lung damage were assessed 84 h after irradiation. Finally, we evaluated the effect of six different IGF-1 dosage regimens administered subcutaneously on gastrointestinal damage and peripheral blood changes in mice 6 days after irradiation (60Co; 12 and 14 Gy; shielded head). The regimens differed in the number of doses (one to five doses) and the onset of administration (starting at 1 [five regimens] or 24 h [one regimen] after irradiation). Results: MTD was established at 1 mg/kg. MTD mitigated lethality induced by 14 Gy and reduced jejunum and lung damage caused by 12 and 14 Gy. However, different dosing regimens showed different efficacy, with three and four doses (administered 1, 24, and 48 h and 1, 24, 48, and 72 h after irradiation, respectively) being the most effective. The three-dose regimens supported intestinal regeneration even if the administration started at 24 h after irradiation, but its potency decreased. Conclusion: IGF-1 seems promising in the mitigation of high-dose irradiation damage. However, the selected dosage regimen affects its efficacy.
- Publikační typ
- časopisecké články MeSH
Hyaluronic acid (HA) has a special position among glycosaminoglycans. As a major component of the extracellular matrix (ECM). This simple, unbranched polysaccharide is involved in the regulation of various biological cell processes, whether under physiological conditions or in cases of cell damage. This review summarizes the history of this molecule's study, its distinctive metabolic pathway in the body, its unique properties, and current information regarding its interaction partners. Our main goal, however, is to intensively investigate whether this relatively simple polymer may find applications in protecting against ionizing radiation (IR) or for therapy in cases of radiation-induced damage. After exposure to IR, acute and belated damage develops in each tissue depending upon the dose received and the cellular composition of a given organ. A common feature of all organ damage is a distinct change in composition and structure of the ECM. In particular, the important role of HA was shown in lung tissue and the variability of this flexible molecule in the complex mechanism of radiation-induced lung injuries. Moreover, HA is also involved in intermediating cell behavior during morphogenesis and in tissue repair during inflammation, injury, and would healing. The possibility of using the HA polymer to affect or treat radiation tissue damage may point to the missing gaps in the responsible mechanisms in the onset of this disease. Therefore, in this article, we will also focus on obtaining answers from current knowledge and the results of studies as to whether hyaluronic acid can also find application in radiation science.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Radiation-associated angiosarcoma (RAAS) is a rare and serious complication of breast irradiation. Due to the rarity of the condition, clinical experience is limited and publications on this topic include only retrospective studies or case reports. MATERIALS AND METHODS: All patients diagnosed with RAAS between January 2000 and December 2017 in twelve centers across the Czech Republic and Slovakia were evaluated. RESULTS: Data of 53 patients were analyzed. The median age at diagnosis was 72 (range 44-89) years. The median latency period between irradiation and diagnosis of RAAS was 78 (range 36-172) months. The median radiation dose was 57.6 (range 34-66) Gy. The whole breast radiation therapy with radiation boost to the tumor bed was the most common radiotherapy regimen. Total mastectomy due to RAAS was performed in 43 patients (81%), radical excision in 8 (15%); 2 patients were not surgically treated due to unresectable disease. Adjuvant chemotherapy followed surgical therapy of RAAS in 18 patients, 3 patients underwent adjuvant radiotherapy. The local recurrence rate of RAAS was 43% and the median time from surgery to the onset of recurrence was 7.5 months (range 3-66 months). The 3-year survival rate was 56%, the 5-year survival rate was only 33%. 46% of patients died during the follow-up period. CONCLUSION: The present data demonstrate that RAAS is a rare condition with high local recurrence rate (43%) and mortality (the 5-year survival rate was 33%.). Early diagnosis of RAAS based on biopsy is crucial for treatment with radical intent. Surgery with negative margins constitutes the most important part of the therapy; the role of adjuvant chemotherapy and radiotherapy is still unclear.
- MeSH
- adjuvantní radioterapie * škodlivé účinky MeSH
- dospělí MeSH
- hemangiosarkom * radioterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mastektomie MeSH
- nádory prsu * radioterapie MeSH
- nádory vyvolané zářením * epidemiologie MeSH
- následné studie MeSH
- retrospektivní studie MeSH
- segmentální mastektomie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Early changes after radiation exposure may serve as predictors as well as targets for alleviation of radiation-induced injury in the lung. The aim of our study was to examine alterations on the cell and tissue levels in the lung and blood changes of immunological and cytokines profiles induced by ionizing radiation (IR) during the first month after irradiation in the mice experimental model. Female C57BL/6 mice were total body irradiated (TBI) by 8 Gy. Lung tissue samples and blood and were collected 4, 8 and 24 h, 7, 21 and 30 d after TBI. We measured absolute cell counts, cell populations and cytokines profile in the blood and evaluated histopathological analysis in the lung, immunophenotypization of the main lung cell populations and cytokine profiles. In blood, the acute radiation syndrome developed with recovery being observed at 21-30 d, observed by hematological markers. In the lung tissue, a biphasic response occurred. At first, a significant decreased of lymphocytes, resident tissues macrophages and air/tissue ratio associated with increased neutrophils was observed at 8 - 24 h. Subsequently, increase in infiltrating CD4+ T-lymphocytes, neutrophils and resident tissues macrophages and decreased airiness were measured 21 and 30 d after TBI. In summary, our study describes the mechanisms that lung tissue enables to cope with non-lethal injury.
Purpose: Among other reasons, the deteriorating global security situation and dangers associated with nuclear weapons have increased the need for deeper knowledge of the basic mechanisms involving the human immune system and ionizing radiation (IR). We conducted a review as to the effects of IR on thymic tissue, and particularly on the development of thymocytes and the T lymphocytes population in peripheral blood. Existing knowledge on this topic is based in part on national registers that store records concerning irradiated people. The majority of studies in this area, however, are based on experimental animal models. The main open question in this subject area regards the delayed effects of IR on thymus tissue, development of thymocytes, and subsequent impact on the immune system. Findings acquired to date on effects of IR are contributing to emerging fields such as immunotherapy, the objective of which is to support or activate natural immunity response. Methods: Recent research articles were reviewed regarding the influence of IR on thymus tissue and thymocytes development. Results: Differentiation and proliferation of thymocytes constitute a complex and sensitive process that is partially altered after irradiation, as are, too, the mechanisms for movement of early (derived from bone marrow) and derived (thymus derivatives) precursors. Disruption of these processes may lead to alteration of immune system function. Conclusions: Low doses (<200 mGy) may lead to changes in or disruption of functions of the thymus, thymocytes, and mechanisms of the immune system. The extent of IR’s influence is dependent not only on the individual’s radiosensitivity but also on his or her sex and age. With increasing absorbed IR dose, the risk of damage to thymus tissue and thymocytes in the organism rises and the extent of damage increases.
- MeSH
- dávka záření MeSH
- hematopoéza účinky záření MeSH
- imunitní systém účinky záření MeSH
- ionizující záření * MeSH
- lidé MeSH
- lymfocyty účinky záření MeSH
- radiační expozice * škodlivé účinky MeSH
- radiační účinky MeSH
- reiradiace MeSH
- thymocyty účinky záření MeSH
- thymus účinky záření MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Purpose: Therapeutic thorax irradiation as an intervention in lung cancer has its limitations due to toxic effects leading to pneumonitis and/or pulmonary fibrosis. It has already been confirmed that hyaluronic acid (HA), an extracellular matrix glycosaminoglycan, is involved in inflammation disorders and wound healing in lung tissue. We examined the effects after gamma irradiation of hyaluronic acid nanoparticles (HANPs) applied into lung prior to that irradiation in a dose causing radiation-induced pulmonary injuries (RIPI). Materials and Methods: Biocompatible HANPs were first used for viability assay conducted on the J774.2 cell line. For in vivo experiments, HANPs were administered intratracheally to C57Bl/6 mice 30 min before thoracic irradiation by 17 Gy. Molecular, cellular, and histopathological parameters were measured in lung and peripheral blood at days 113, 155, and 190, corresponding to periods of significant morphological and/or biochemical alterations of RIPI. Results: Modification of linear hyaluronic acid molecule into nanoparticles structure significantly affected the physiological properties and caused long-term stability against ionizing radiation. The HANPs treatments had significant effects on the expression of the cytokines and particularly on the pro-fibrotic signaling pathway in the lung tissue. The radiation fibrosis phase was altered significantly in comparison with a solely irradiated group. Conclusions: The present study provides evidence that application of HANPs caused significant changes in molecular and cellular patterns associated with RIPI. These findings suggest that HANPs could diminish detrimental radiation-induced processes in lung tissue, thereby potentially decreasing the extracellular matrix degradation leading to lung fibrosis.
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
