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1.
J Radiol Prot ; 43(4)2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38035396

RESUMO

An anonymous web-based survey was developed to check different aspects (SHAMISEN SINGS project): stakeholder awareness and perceptions of available mobile applications (apps) for measuring ionising radiation doses and health/well-being indicators; whether they would be ready to use them in the post-accidental recovery; and what are their preferred methodologies to acquire information etc. The results show that participation of the citizens would be most beneficial during post-accident recovery, providing individual measurements of external ionizing dose and health/well-being parameters, with possible follow-up. Also, participants indicated different preferences for sources to gain knowledge on ionising radiation and for the functions that an ideal app should have. The level of awareness and readiness to use apps to measure ionising radiation dose depended on two main aspects: individual differences (age & gender) and whether people were from countries affected by the previous major accidents. We concluded that stakeholders could have benefits from the data management plan: (1) it potentiates resilience at individual and community level; (2) citizens' measurements contribute to environmental monitoring and public health screening; (3) linkages between different types of data (environmental exposure, individual behavioural diaries, and measurements of health indicators) allow to perform more rigorous epidemiological studies.


Assuntos
Telefone Celular , Aplicativos Móveis , Liberação Nociva de Radioativos , Resiliência Psicológica , Humanos , Exposição Ambiental
2.
Biology (Basel) ; 11(8)2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-36009820

RESUMO

Radiation therapy is widely used as an anti-neoplastic treatment despite the adverse effects it can cause in non-tumoral tissues. Radiosensitizing agents, which can increase the effect of radiation in tumor cells, such as gold nanoparticles (GNPs), have been described. To evaluate the radiosensitizing effect of 50 nm GNPs, we carried out a series of studies in two neoplastic cell lines, Caco2 (colon adenocarcinoma) and SKBR3 (breast adenocarcinoma), qualitatively evaluating the internalization of the particles, determining with immunofluorescence the number of γ-H2AX foci after irradiation with ionizing radiation (3 Gy) and evaluating the viability rate of both cell lines after treatment by means of an MTT assay. Nanoparticle internalization varied between cell lines, though they both showed higher internalization degrees for functionalized GNPs. The γ-H2AX foci counts for the different times analyzed showed remarkable differences between cell lines, although they were always significantly higher for functionalized GNPs in both lines. Regarding cell viability, in most cases a statistically significant decreasing tendency was observed when treated with GNPs, especially those that were functionalized. Our results led us to conclude that, while 50 nm GNPs induce a clear radiosensitizing effect, it is highly difficult to describe the magnitude of this effect as universal because of the heterogeneity found between cell lines.

3.
Environ Int ; 146: 106175, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33069983

RESUMO

The experiences of the Chernobyl and Fukushima nuclear accidents showed that dosimetry was the essential tool in the emergency situation for decision making processes, such as evacuation and application of protective measures. However, at the consequent post-accidental phases, it was crucial also for medical health surveillance and in further adaptation to changed conditions with regards to radiation protection of the affected populations. This review provides an analysis of the experiences related to the role of dosimetry (dose measurements, assessment and reconstruction) regarding health preventive measures in the post-accidental periods on the examples of the major past nuclear accidents such as Chernobyl and Fukushima. Recommendations derived from the review are called to improve individual dose assessment in case of a radiological accident/incident and should be considered in advance as guidelines to follow for having better information. They are given as conclusions.


Assuntos
Acidente Nuclear de Chernobyl , Acidente Nuclear de Fukushima , Monitoramento de Radiação , Proteção Radiológica , Humanos , Japão
4.
Antioxidants (Basel) ; 9(9)2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32825731

RESUMO

The purpose of this study was to evaluate the relationship between blood redox status, dose and antioxidant dietary intake of different hospital staff groups exposed to low doses of ionizing radiation (LDIR) (Interventional Radiology and Cardiology, Radiation Oncology, and Nuclear Medicine) and non-exposed. Personal dose equivalent (from last year and cumulative), plasma antioxidant markers (total antioxidant capacity, extracellular superoxide dismutase activity, and glutathione/oxidized glutathione ratio), oxidative stress markers (nitrites and nitrates, and lipid peroxidation) and dietary intake (antioxidant capacity using ORAC values) were collected and analyzed from 28 non-exposed healthcare workers and 42 healthcare workers exposed to LDIR. Hospital staff exposed to LDIR presented a redox imbalance in blood that seems to correlate with dose. Workers from the Nuclear Medicine Unit were the most affected group with the lowest value of plasma antioxidant response and the highest value of plasma thiobarbituric acid reactive substances, TBARS (indicator of lipid peroxidation) of all four groups. Cumulative personal dose equivalent positively correlated with nitrites and negatively correlated with total antioxidant capacity in blood. The diet of healthcare workers from Nuclear Medicine Unit had higher ORAC values than the diet of non-exposed. Therefore, occupational exposure to LDIR, especially for the Nuclear Medicine Unit, seems to produce an imbalanced redox status in blood that would correlate with cumulative personal dose equivalent.

5.
Radiat Res ; 191(6): 566-584, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31021733

RESUMO

Advances in accelerator technology, which have enabled conforming radiotherapy with charged hadronic species, have brought benefits as well as potential new risks to patients. To better understand the effects of ionizing radiation on tumor and surrounding tissue, it is important to investigate and quantify the relationship between energy deposition at the nanometric scale and the initial biological events. Monte Carlo track structure simulation codes provide a powerful tool for investigating this relationship; however, their success and reliability are dependent on their improvement and development accordingly to the dedicated biological data to which they are challenged. For this aim, a microbeam facility that allows for fluence control, down to one ion per cell nucleus, was used to evaluate relative frequencies of DNA damage after interaction between the incoming ion and DNA according to radiation quality. Primary human cells were exposed to alpha particles of three different energies with respective linear energy transfers (LETs) of approximately 36, 85 or 170 keV·µm-1 at the cells' center position, or to protons (19 keV·µm-1). Statistical evaluation of nuclear foci formation (53BP1/γ-H2AX), observed using immunofluorescence and related to a particle traversal, was undertaken in a large population of cell nuclei. The biological results were adjusted to consider the factors that drive the experimental uncertainties, then challenged with results using Geant4-DNA code modeling of the ionizing particle interactions on a virtual phantom of the cell nucleus with the same mean geometry and DNA density as the cells used in our experiments. Both results showed an increase of relative frequencies of foci (or simulated DNA damage) in cell nuclei as a function of increasing LET of the traversing particles, reaching a quasi-plateau when the LET exceeded 80-90 keV·µm-1. For the LET of an alpha particle ranging from 80-90 to 170 keV·µm-1, 10-30% of the particle hits did not lead to DNA damage inducing 53BP1 or γ-H2AX foci formation.


Assuntos
Dano ao DNA , Transferência Linear de Energia/genética , Método de Monte Carlo , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação , Núcleo Celular/metabolismo , Núcleo Celular/efeitos da radiação , Histonas/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos da radiação , Humanos , Modelos Biológicos , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo
6.
Sci Rep ; 9(1): 150, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30655613

RESUMO

One of the most severe complications after successful cancer therapy is the development of therapy-related myeloid neoplasms (t-MN). Constitutional genetic variation is likely to impact on t-MN risk. We aimed to evaluate if polymorphisms in the p53 pathway can be useful for predicting t-MN susceptibility. First, an association study revealed that the Pro variant of the TP53 Arg72Pro polymorphism and the G allele of the MDM2 SNP309 were associated with t-MN risk. The Arg variant of TP53 is more efficient at inducing apoptosis, whereas the Pro variant is a more potent inductor of cell cycle arrest and DNA repair. As regards MDM2 SNP309, the G allele is associated with attenuation of the p53 apoptotic response. Second, to evaluate the biological effect of the TP53 polymorphism, we established Jurkat isogenic cell lines expressing p53Arg or p53Pro. Jurkat p53Arg cells presented higher DNA damage and higher apoptotic potential than p53Pro cells, after treatment with chemotherapy agents. Only p53Pro cells presented t(15;17) translocation and del(5q). We suggest that failure to repair DNA lesions in p53Arg cells would lead them to apoptosis, whereas some p53Pro cells, prone to cell cycle arrest and DNA repair, could undergo misrepair, generating chromosomal abnormalities typical of t-MN.


Assuntos
Leucemia/tratamento farmacológico , Segunda Neoplasia Primária/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína Supressora de Tumor p53/genética , Feminino , Predisposição Genética para Doença , Humanos , Células Jurkat , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco
7.
Oncotarget ; 9(44): 27397-27411, 2018 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-29937993

RESUMO

The aim of this study was to carry out a comprehensive examination of potential genotoxic effects of low doses of tritium delivered chronically to mice and to compare these effects to the ones resulting from equivalent doses of gamma-irradiation. Mice were chronically exposed for one or eight months to either tritiated water (HTO) or organically bound tritium (OBT) in drinking water at concentrations of 10 kBq/L, 1 MBq/L or 20 MBq/L. Dose rates of internal ß-particle resulting from such tritium treatments were calculated and matching external gamma-exposures were carried out. We measured cytogenetic damage in bone marrow and in peripheral blood lymphocytes (PBLs) and the cumulative tritium doses (0.009 - 181 mGy) were used to evaluate the dose-response of OBT in PBLs, as well as its relative biological effectiveness (RBE). Neither tritium, nor gamma exposures produced genotoxic effects in bone marrow. However, significant increases in chromosome damage rates in PBLs were found as a result of chronic OBT exposures at 1 and 20 M Bq/L, but not at 10 kBq/L. When compared to an external acute gamma-exposure ex vivo, the RBE of OBT for chromosome aberrations induction was evaluated to be significantly higher than 1 at cumulative tritium doses below 10 mGy. Although found non-existent at 10 kBq/L (the WHO limit), the genotoxic potential of low doses of tritium (>10 kBq/L), mainly OBT, may be higher than currently assumed.

8.
Int J Radiat Biol ; 94(3): 248-258, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29363380

RESUMO

PURPOSE: The fluorescent in situ hybridization (FISH) technique, which easily detects reciprocal translocations, is currently used to estimate doses in retrospective biological dosimetry, after suspected accidental overexposure to ionizing radiation (IR). This study of 42 cases aimed to verify the appropriateness of this assay for radiation dose reconstruction, compared to the dicentric assay, and to evaluate other limitations. MATERIAL AND METHODS: We labeled chromosomes 2, 4, and 12 by 3-color FISH painting to detect translocations on lymphocytes of patients with suspected past IR overexposure. RESULT: Translocation dose estimation showed doses significantly different from 0 Gy in 25 of the 42 cases. The lowest positive dose measured was 0.3 Gy. Several months after IR exposure, the doses measured by translocation and dicentric assays are quite similar. For a year, dose estimation by translocation assay becomes more relevant as dicentric frequency starts to decrease, coming close to 0 for more than a year after the exposure. The persistence of translocations enabled us to corroborate an overexposure 44 years earlier. Interpretation of the observed translocation yield requires the knowledge of the patient's other radiation exposures. A dose assessment by this biomarker is relevant only if the radiation exposure is confirmed. CONCLUSIONS: This technique is appropriate for corroborating a former IR exposure of individuals. When the radiation dose is greater than 1 Gy, the translocations in complex exchanges must be considered. Another relevant point is the use of an appropriate background yield of translocations. The dose assessment, however, also depends on exposure to various genotoxic agents besides IR. If no evidence about the existence of radiation exposure is available, dose assessment is not useful. For this reason, report only the translocation frequency and its comparison with the background yield by age class is preferable.


Assuntos
Hibridização in Situ Fluorescente , Radiometria/métodos , Translocação Genética/efeitos da radiação , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
9.
Mutat Res ; 797-799: 15-25, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28340407

RESUMO

Unrepaired DNA double-strand breaks (DSBs) induced by ionizing radiation are associated with lethal effects and genomic instability. After the initial breaks and chromatin destabilization, a set of post-translational modifications of histones occurs, including phosphorylation of serine 139 of histone H2AX (γH2AX), which leads to the formation of ionizing radiation-induced foci (IRIF). DSB repair results in the disappearance of most IRIF within hours after exposure, although some remain 24h after irradiation. Their relation to unrepaired DSBs is generally accepted but still controversial. This study evaluates the frequency and kinetics of persistent IRIF and analyzes their impact on cell proliferation. We observed persistent IRIF up to 7 days postirradiation, and more than 70% of cells exposed to 5Gy had at least one of these persistent IRIF 24h after exposure. Moreover we demonstrated that persistent IRIF did not block cell proliferation definitively. The frequency of IRIF was lower in daughter cells, due to asymmetric distribution of IRIF between some of them. We report a positive association between the presence of IRIF and the likelihood of DNA missegregation. Hence, the structure formed after the passage of a persistent IRI focus across the S and G2 phases may impede the correct segregation of the affected chromosome's sister chromatids. The ensuing abnormal resolution of anaphase might therefore cause the nature of IRIF in daughter-cell nuclei to differ before and after the first cell division. The resulting atypical chromosomal assembly may be lethal or result in a gene dosage imbalance and possibly enhanced genomic instability, in particular in the daughter cells.


Assuntos
Ciclo Celular/efeitos da radiação , Quebras de DNA de Cadeia Dupla , DNA/efeitos da radiação , Histonas/genética , Radiação Ionizante , Ciclo Celular/genética , Relação Dose-Resposta à Radiação , Feminino , Fase G1/genética , Fase G1/efeitos da radiação , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Cultura Primária de Células , Fase de Repouso do Ciclo Celular/genética , Fase de Repouso do Ciclo Celular/efeitos da radiação , Fatores de Tempo
10.
Int J Radiat Biol ; 93(1): 127-135, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27572921

RESUMO

PURPOSE: Reliable dose estimation is an important factor in appropriate dosimetric triage categorization of exposed individuals to support radiation emergency response. MATERIALS AND METHODS: Following work done under the EU FP7 MULTIBIODOSE and RENEB projects, formal methods for defining uncertainties on biological dose estimates are compared using simulated and real data from recent exercises. RESULTS: The results demonstrate that a Bayesian method of uncertainty assessment is the most appropriate, even in the absence of detailed prior information. The relative accuracy and relevance of techniques for calculating uncertainty and combining assay results to produce single dose and uncertainty estimates is further discussed. CONCLUSIONS: Finally, it is demonstrated that whatever uncertainty estimation method is employed, ignoring the uncertainty on fast dose assessments can have an important impact on rapid biodosimetric categorization.


Assuntos
Algoritmos , Bioensaio/métodos , Exposição à Radiação/análise , Monitoramento de Radiação/métodos , Triagem/métodos , Teorema de Bayes , Europa (Continente) , Humanos , Guias de Prática Clínica como Assunto , Doses de Radiação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
Int J Radiat Biol ; 93(1): 2-14, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27707245

RESUMO

PURPOSE: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios. RESULTS: The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. CONCLUSIONS: RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.


Assuntos
Bioensaio/métodos , Planejamento em Desastres/organização & administração , Lesões por Radiação/prevenção & controle , Monitoramento de Radiação/métodos , Proteção Radiológica/métodos , Gestão da Segurança/organização & administração , Emergências , Europa (Continente) , Humanos , Objetivos Organizacionais , Exposição à Radiação/análise , Exposição à Radiação/prevenção & controle , Liberação Nociva de Radioativos/prevenção & controle
12.
Sci Rep ; 6: 27043, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27245205

RESUMO

Normal tissue toxicity after radiotherapy shows variability between patients, indicating inter-individual differences in radiosensitivity. Genetic variation probably contributes to these differences. The aim of the present study was to determine if two cell lines, one radiosensitive (RS) and another radioresistant (RR), showed differences in DNA repair capacity, cell viability, cell cycle progression and, in turn, if this response could be characterised by a differential gene expression profile at different post-irradiation times. After irradiation, the RS cell line showed a slower rate of γ-H2AX foci disappearance, a higher frequency of incomplete chromosomal aberrations, a reduced cell viability and a longer disturbance of the cell cycle when compared to the RR cell line. Moreover, a greater and prolonged transcriptional response after irradiation was induced in the RS cell line. Functional analysis showed that 24 h after irradiation genes involved in "DNA damage response", "direct p53 effectors" and apoptosis were still differentially up-regulated in the RS cell line but not in the RR cell line. The two cell lines showed different response to IR and can be distinguished with cell-based assays and differential gene expression analysis. The results emphasise the importance to identify biomarkers of radiosensitivity for tailoring individualized radiotherapy protocols.


Assuntos
Linfócitos B/efeitos da radiação , Ciclo Celular/efeitos da radiação , Reparo do DNA/efeitos da radiação , Regulação da Expressão Gênica/efeitos da radiação , Transcrição Gênica/efeitos da radiação , Adaptação Fisiológica , Linfócitos B/citologia , Linfócitos B/metabolismo , Ciclo Celular/genética , Morte Celular/efeitos da radiação , Linhagem Celular Transformada , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Relação Dose-Resposta à Radiação , Raios gama/efeitos adversos , Perfilação da Expressão Gênica , Histonas/genética , Histonas/metabolismo , Humanos , Anotação de Sequência Molecular , Tolerância a Radiação , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
13.
Radiat Environ Biophys ; 55(2): 203-13, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27015828

RESUMO

The purpose of this study was to compare cytogenetic data in a patient before and after treatment with radioiodine to evaluate the assays in the context of biological dosimetry. We studied a 34-year-old male patient who underwent a total thyroidectomy followed by ablation therapy with (131)I (19.28 GBq) for a papillary thyroid carcinoma. The patient provided blood samples before treatment and then serial samples at monthly intervals during the first year period and quarterly intervals for 5 years and finally 20 years after treatment. A micronucleus assay, dicentric assay, FISH method and G-banding were used to detect and measure DNA damage in circulating peripheral blood lymphocytes of the patient. The results showed that radiation-induced cytogenetic effects persisted for many years after treatment as shown by elevated micronuclei and chromosome aberrations as a result of exposure to (131)I. At 5 years after treatment, the micronucleus count was tenfold higher than the pre-exposure frequency. Shortly after the treatment, micronucleus counts produced a dose estimate of 0.47 ± 0.09 Gy. The dose to the patient evaluated retrospectively using FISH-measured translocations was 0.70 ± 0.16 Gy. Overall, our results show that the micronucleus assay is a retrospective biomarker of low-dose radiation exposure. However, this method is not able to determine local dose to the target tissue which in this case was any residual thyroid cells plus metastases of thyroidal origin.


Assuntos
Análise Citogenética , Radioisótopos do Iodo/efeitos adversos , Lesões por Radiação/genética , Adulto , Carcinoma/genética , Carcinoma/radioterapia , Carcinoma/cirurgia , Carcinoma Papilar , Aberrações Cromossômicas/efeitos da radiação , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Radioisótopos do Iodo/uso terapêutico , Cariótipo , Masculino , Testes para Micronúcleos , Medição de Risco , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
14.
Radiat Environ Biophys ; 55(1): 61-70, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26781448

RESUMO

In case of external overexposure to ionizing radiation, an estimation of its genotoxic effects on exposed individuals can be made retrospectively by the measurement of radiation-induced chromosome aberrations on circulating lymphocytes. Compared with external irradiation, intakes of radionuclides may, however, lead to specific features influencing dose distribution at the scale of body, of tissue or even of cell. Therefore, in case of internal contamination by radionuclides, experimental studies, particularly using animal models, are required to better understand mechanisms of their genotoxic effects and to better estimate the absorbed dose. The present study was designed to evaluate a cytogenetic method in mouse peripheral blood lymphocytes that would allow determination of yields and complexities of chromosome aberrations after low-dose rate exposure to (137)Cs delivered in vitro either by irradiation or by contamination. By using M-FISH analysis, we compared the low-dose rate responses observed in mouse to the high-dose rate responses observed both in mouse and in human. Promising similarities between the two species in the relative biological effect evaluation show that our cytogenetic model established in mouse might be useful to evaluate various radiation exposures, particularly relevant in case of intakes of radionuclides.


Assuntos
Radioisótopos de Césio/efeitos adversos , Análise Citogenética , Linfócitos/citologia , Linfócitos/efeitos da radiação , Animais , Aberrações Cromossômicas/efeitos da radiação , Relação Dose-Resposta a Droga , Raios gama/efeitos adversos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
15.
Radiat Res ; 185(2): 151-62, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26771173

RESUMO

In biological dosimetry by dicentric analysis, an exposure to radiation is considered non-homogeneous if the dicentric cell distribution shows overdispersion with respect to Poisson distribution. Traditionally, when this occurs, all non-homogeneous exposures are considered as partial-body exposures, assuming that there is only a mixture of irradiated and nonirradiated cells. The methods to estimate the dose in the irradiated fraction and the initial fraction of irradiated cells are based on separating which part of the cells without aberrations comes from the nonirradiated or irradiated fractions. In this study we show a new approach based on a mixed Poisson model, which allows for a distinction to be made between partial and heterogeneous exposures. To validate this approach blood samples from two donors, a male and a female, irradiated at different doses, were mixed at a 1:1 proportion to simulate partial and heterogeneous exposures. The results show a good agreement between the observed proportion of male and female cells and the proportion estimated by the model. Additionally, a good agreement was observed between the delivered doses, the initial fraction of cells and the ones estimated by the model. This good agreement was also observed after very high-dose irradiation (up to 17 Gy), when the lymphocyte cultures were treated with caffeine. Based on these results, we propose the use of this mixed Poisson model for a more accurate assessment of non-homogeneous exposures.


Assuntos
Bioensaio/métodos , Aberrações Cromossômicas/efeitos da radiação , Leucócitos Mononucleares/fisiologia , Leucócitos Mononucleares/efeitos da radiação , Modelos Biológicos , Monitoramento de Radiação/métodos , Adulto , Células Cultivadas , Simulação por Computador , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Doses de Radiação , Exposição à Radiação , Radiação Ionizante , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
PLoS One ; 11(1): e0145786, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26727594

RESUMO

Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF) per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This comparison allowed us to calculate a volume of 1.6 µm3 for which the spread of the specific energy distribution could explain the entire variability of RIF counts per cell in an exposed cell population. The definition of this volume may allow to use a microdosimetric quantity to predict heterogeneity in DNA damage. Moreover, this value is consistent with the order of magnitude of the volume occupied by the hydrated sugar-phosphate backbone of the DNA molecule, which is the part of the DNA molecule responsible for strand breaks.


Assuntos
Dano ao DNA , DNA/efeitos da radiação , Histonas/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos
17.
Genet Test Mol Biomarkers ; 20(2): 94-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26716824

RESUMO

BACKGROUND: A combination of several factors including a change in the paint application system; a lack of proper hygiene; and inadequate safety measures caused a severe health impact in the workers of some textile painting factories. This outbreak, mainly characterized by respiratory disorders, caused the death of six people and it has been classified as Ardystil syndrome. MATERIALS AND METHODS: Fifty-two workers involved in the outbreak and 48 healthy subjects not known to have exposed to the potentially mutagenic agents participated in the study. The program evaluated possible genotoxic damage through the sister chromatid exchange (SCE) cytogenetic biomarker assay. We determined the frequency of SCE, high-frequency cells (HFCs), and a ratio, which can be considered as a new parameter, allowing for the study of the SCE distribution pattern among the chromosomes. RESULTS: There was no statistically significant difference in the SCE frequency and in the mean number of HFCs between the control and the Ardystil-affected groups. However, smoking increased the incidence of all parameters studied in both the case and control groups. CONCLUSIONS: This study shows that workers involved in the Ardystil syndrome did not suffer genotoxic damage as measured by SCE and HFCs when compared with the control group.


Assuntos
Dano ao DNA , Exposição Ocupacional/efeitos adversos , Transtornos Respiratórios/genética , Troca de Cromátide Irmã/genética , Indústria Têxtil , Feminino , Humanos , Masculino , Transtornos Respiratórios/induzido quimicamente , Síndrome
18.
Int J Radiat Biol ; 91(12): 915-24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26489383

RESUMO

PURPOSE: The number of radio-induced double-strand breaks is correlated with the number of histone gamma-H2AX (γ-H2AX) foci. For this reason, foci quantification is a useful tool to measure radiation-induced DNA damage and the number of foci has been suggested as a predictive biomarker of radiosensitivity. The aim of the present study was to evaluate the reproducibility of different microscopic methodologies and flow cytometry analysis to score γ-H2AX induction, and its suitability to distinguish a radiosensitive (RS) cell line from a radioresistant (RR) one. MATERIALS AND METHODS: γ-H2AX analyses were performed by semi-automated and automated microscopic methods and by flow cytometry before and after irradiation in two human lymphoblastoid cell lines and in lymphocytes from three healthy donors. RESULTS: Reproducible results were obtained by all the methodologies tested, although not all showed the same sensitivity. The RS cell line always showed higher foci counts and higher levels of immunofluorescence intensity after irradiation than the RR cell line. CONCLUSIONS: Our results suggest that microscopic methodologies with z-stage capacity give the most accurate results after 1 Gy irradiation. However, for high doses of ionizing radiation, flow cytometry gives reliable results. Further studies will be necessary to determine the usefulness of γ-H2AX analysis to predict adverse side reactions in radiotherapy patients.


Assuntos
Citometria de Fluxo/métodos , Histonas/metabolismo , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Tolerância a Radiação , Linhagem Celular Tumoral , Humanos , Processamento de Imagem Assistida por Computador , Linfócitos/metabolismo , Linfócitos/efeitos da radiação , Fosforilação/efeitos da radiação
19.
J Radiat Res ; 56(4): 709-16, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25922373

RESUMO

Two cases of hematological malignancies were reported in an industrial radiography company over a year, which were reasonably suspected of being consequences of prolonged exposure to ionizing radiation because of the higher incidence than expected in the general population. We analyzed chromosomal aberrations in the peripheral blood lymphocytes from the other workers who had been working under similar circumstances as the patients in the company. Among the subjects tested, 10 workers who belonged to the highest band were followed up periodically for 1.5 years since the first analysis. The aim of this study was to clarify pertinence of translocation analysis to an industrial set-up where chronic exposure was commonly expected. To be a useful tool for a retrospective biodosimetry, the aberrations need to be persistent for a decade or longer. Therefore we calculated the decline rates and half-lives of frequency for both a reciprocal translocation and a dicentric chromosome and compared them. In this study, while the frequency of reciprocal translocations was maintained at the initial level, dicentric chromosomes were decreased to 46.9% (31.0-76.5) of the initial frequency over the follow-up period. Our results support the long-term stability of reciprocal translocation through the cell cycle and validate the usefulness of translocation analysis as a retrospective biodosimetry for cases of occupational exposure.


Assuntos
Bioensaio/métodos , Aberrações Cromossômicas/efeitos da radiação , Exposição Ocupacional/análise , Exposição à Radiação/análise , Radiometria/métodos , Translocação Genética/efeitos da radiação , Adulto , Técnicas Biossensoriais/métodos , Relação Dose-Resposta à Radiação , Humanos , Leucócitos Mononucleares/fisiologia , Leucócitos Mononucleares/efeitos da radiação , Masculino , Doses de Radiação , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Translocação Genética/genética
20.
Food Chem Toxicol ; 66: 107-12, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24444548

RESUMO

According to the International Agency for Research on Cancer, smoking tobacco is a major cause of cancer in humans. It causes about half of all male cancer deaths and an ever increasing number of cancer deaths in females. The aim of this study was to establish whether cigarette smoking increases sister chromatid exchanges (SCEs) in peripheral blood lymphocytes in two Spanish population groups; light and heavy smokers. The mean number of High-Frequency Cells (HFCs) was determined and, the SCE distribution pattern among the chromosomes was analysed represented by a ratio described below. A local sample of 101 adult smokers (n=48) and non-smokers (n=53), aged from 18 to 49 years, was studied using SCE levels in peripheral lymphocytes. Heavy smoking (≥ 10 cigarettes per day) increased significantly the SCE frequency and the HFC parameters. Neither age nor sex significantly influenced the frequencies in the groups studied.


Assuntos
Linfócitos/ultraestrutura , Troca de Cromátide Irmã , Fumar/genética , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espanha , Adulto Jovem
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