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: 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
The goal of this study was to develop novel radioprotective agents targeting the intrinsic apoptotic pathway and thus decreasing the radiation-induced damage. For that purpose, we designed, synthesized and analyzed ten new compounds based on the 1-(4-(2-hydroxyethyl)piperazin-1-yl)-3-phenoxypropan-2-ol leading structure. The cytotoxicity of the newly synthesized substances was tested in vitro on cell lines derived from different progenitor cells by WST-1 proliferation assay. MTT test was utilized to assess half-maximal inhibitory concentrations and maximum tolerated concentrations of novel compounds in A-549 cells. Screening for radioprotective properties was performed using flow-cytometry in MOLT-4 cells exposed to 60Co ionizing gamma radiation. Selected candidates underwent in vivo testing in C57Bl/6 J mice having a positive impact on their immunological status. In summary, we report here promising compounds with radioprotective effect in vivo.
- MeSH
- apoptóza účinky léků MeSH
- knihovny malých molekul chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- molekulární struktura MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- propanoly chemická syntéza chemie farmakologie MeSH
- radioprotektivní látky chemická syntéza chemie farmakologie MeSH
- simulace molekulového dockingu MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The aim of the present study was to evaluate the biodosimetric potential of peripheral blood lymphocytes, particularly of T-cell subsets (null and T helper) and natural killer cells (NK), upon exposure to gamma irradiation (60Co) in vivo. For this purpose, the change in relative numbers of NK cells and T-lymphocyte subsets, as well as in the H2AX phosphorylation rate, were evaluated as potential early markers of the lymphocytic response to irradiation in vivo. These experiments were performed on a Large White Pig model. As a result, significant but not dose-dependent changes in the proportion of lymphocyte subpopulations (NK cells, null and T helper cells) were found after exposure to ionising radiation in vivo. On the other hand, circulating NK cells showed relatively higher radioresistance capacity when compared to the T-lymphocyte subsets; however, gamma-H2AX expression showed no significant difference between the evaluated lymphocyte subsets.
- MeSH
- buňky NK účinky záření MeSH
- fenotyp MeSH
- fosforylace MeSH
- histony metabolismus MeSH
- imunofenotypizace MeSH
- ionizující záření MeSH
- lymfocyty cytologie MeSH
- poškození DNA MeSH
- prasata MeSH
- radioizotopy kobaltu farmakologie MeSH
- radiometrie metody MeSH
- T-lymfocyty - podskupiny účinky záření MeSH
- záření gama MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The increasing risk of acute large-scale exposure of ionising irradiation on the population underlines the necessity of developing effective radioprotective and mitigating agents. The aim of this work was to investigate the effect of sodium orthovanadate pre-treatment on mice exposed to high doses of gamma rays (from 5 to 13 Gy). The determination of median lethal dose within 30 days confirmed that orthovanadate applied to total-body-irradiated mice intra-peritoneally has a radioprotective but not a mitigating effect. With orthovanadate pre-treatment, the composition of cellularity in the bone marrow improved substantially and the main lymphocyte populations restored during the first month after irradiation. These findings contribute to 'gap-filling' in radioprotective effects and demonstrate the importance of haematological parameters in radiation-response prediction.
- MeSH
- B-lymfocyty účinky léků MeSH
- buňky NK účinky léků MeSH
- celotělové ozáření * MeSH
- inhibitor p21 cyklin-dependentní kinasy metabolismus MeSH
- ionizující záření MeSH
- kostní dřeň účinky léků účinky záření MeSH
- lymfocyty účinky léků účinky záření MeSH
- makrofágy metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- průtoková cytometrie MeSH
- radioprotektivní látky farmakologie MeSH
- T-lymfocyty účinky léků MeSH
- vanadáty farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
