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1.
Sci Rep ; 14(1): 8468, 2024 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605022

RESUMO

Spatially Fractionated Radiotherapy (SFRT) has demonstrated promising potential in cancer treatment, combining the advantages of reduced post-radiation effects and enhanced local control rates. Within this paradigm, proton minibeam radiotherapy (pMBRT) was suggested as a new treatment modality, possibly producing superior normal tissue sparing to conventional proton therapy, leading to improvements in patient outcomes. However, an effective and convenient beam generation method for pMBRT, capable of implementing various optimum dose profiles, is essential for its real-world application. Our study investigates the potential of utilizing the moiré effect in a dual collimator system (DCS) to generate pMBRT dose profiles with the flexibility to modify the center-to-center distance (CTC) of the dose distribution in a technically simple way.We employ the Geant4 Monte Carlo simulations tool to demonstrate that the angle between the two collimators of a DCS can significantly impact the dose profile. Varying the DCS angle from 10 ∘ to 50 ∘ we could cover CTC ranging from 11.8 mm to 2.4 mm, respectively. Further investigations reveal the substantial influence of the multi-slit collimator's (MSC) physical parameters on the spatially fractionated dose profile, such as period (CTC), throughput, and spacing between MSCs. These findings highlight opportunities for precision dose profile adjustments tailored to specific clinical scenarios.The DCS capacity for rapid angle adjustments during the energy transition stages of a spot scanning system can facilitate dynamic alterations in the irradiation profile, enhancing dose contrast in normal tissues. Furthermore, its unique attribute of spatially fractionated doses in both lateral directions could potentially improve normal tissue sparing by minimizing irradiated volume. Beyond the realm of pMBRT, the dual MSC system exhibits remarkable versatility, showing compatibility with different types of beams (X-rays and electrons) and applicability across various SFRT modalities.Our study illuminates the dual MSC system's potential as an efficient and adaptable tool in the refinement of pMBRT techniques. By enabling meticulous control over irradiation profiles, this system may expedite advancements in clinical and experimental applications, thereby contributing to the evolution of SFRT strategies.


Assuntos
Terapia com Prótons , Lesões por Radiação , Humanos , Terapia com Prótons/métodos , Prótons , Radiação Ionizante , Método de Monte Carlo , Etoposídeo , Fracionamento da Dose de Radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
2.
J Radiol Prot ; 44(2)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38569480

RESUMO

The number of healthcare workers occupationally exposed to ionizing radiation (IR) is increasing every year. As health effects from exposure to low doses IR have been reported, radiation protection (RP) in the context of occupational activities is a major concern. This study aims to assess the compliance of healthcare workers with RP policies, according to their registered cumulative dose, profession, and perception of radiation self-exposure and associated risk. Every healthcare worker from one of the participating hospitals in France with at least one dosimetric record for each year 2009, 2014, and 2019 in the SISERI registry was included and invited to complete an online questionnaire including information on the worker's occupational exposure, perception of IR-exposure risk and RP general knowledge. Hp(10) doses were provided by the SISERI system. Multivariate logistic regressions were used. Dosimeter wearing and RP practices compliance were strongly associated with 'feeling of being IR-exposed' (OR = 3.69, CI95% 2.04-6.66; OR = 4.60, CI95% 2.28-9.30, respectively). However, none of these factors was associated with RP training courses attendance. The main reason given for non-compliance is unsuitability or insufficient numbers of RP devices. This study provided useful information for RP policies. Making exposed workers aware of their own IR-exposure seems to be a key element to address in RP training courses. This type of questionnaire should be introduced into larger epidemiological studies. Dosimeter wearing and RP practices compliance are associated to feeling being IR-exposed. RP training courses should reinforce workers' awareness of their exposure to IR.


Assuntos
Exposição Ocupacional , Proteção Radiológica , Humanos , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Radiometria , Radiação Ionizante , Hospitais , Exposição Ocupacional/prevenção & controle , Exposição Ocupacional/análise
3.
Sud Med Ekspert ; 67(2): 39-42, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38587157

RESUMO

A rare clinical observation of death from prolonged uneven external irradiation due to the deliberate use of an ionizing radiation source for illegal purposes has been presented. The main difficulties of postmortem diagnosis of this type of radiation-induced injury, considering the features of histological examinations and special methods of retrospective dosimetric evaluations, have been identified.


Assuntos
Radiação Ionizante , Estudos Retrospectivos
4.
Rev Bras Epidemiol ; 27: e240011, 2024.
Artigo em Inglês, Português | MEDLINE | ID: mdl-38511821

RESUMO

OBJECTIVE: To compare cancer mortality among workers exposed to gamma and X radiation and the general population of the city of São Paulo, as well as that of the subgroup monitored with those not monitored for gamma and X radiation in a work unit with ionizing radiation based in the city of São Paulo. METHODS: Between 2016 and 2021, a retrospective open cohort study was carried out with workers who were employed from 08/31/1956 to 12/31/2016 based on data collected at the company and in official institutions. Standardized mortality ratios (SMR) were calculated by sex, age and calendar period of cancers grouped according to type, risk factor and organ system in two analyses: in the external analysis, the mortality of the study population was compared with that of the general population of the city of São Paulo; In the internal analysis, the mortality of the monitored subgroup was compared with that of the subgroup not monitored for gamma and X radiation. RESULTS: The external mortality analysis showed SMR=0.224 (95%CI 0.208-0.240) and the healthy worker effect, while the internal mortality analysis showed SMR=0.685 (95%CI 0.618-0.758). CONCLUSION: This study showed lower cancer mortality among exposed workers when compared to mortality in the general population and the healthy worker effect. Among workers monitored for gamma and X radiation, cancer mortality was lower when compared to those not monitored.


Assuntos
Neoplasias , Doenças Profissionais , Exposição Ocupacional , Humanos , Estudos de Coortes , Estudos Retrospectivos , Brasil/epidemiologia , Radiação Ionizante , Exposição Ocupacional/efeitos adversos , Doenças Profissionais/etiologia
5.
J Cancer Res Ther ; 20(1): 126-132, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38554309

RESUMO

BACKGROUND: The Ccr4-Not complex (CNOT complex in mammals) is a unique and highly conserved complex with numerous cellular functions. Until now, there has been relatively little known about the importance of the CNOT complex subunits in the DNA damage response (DDR) in mammalian cells. CNOT4 is a subunit of the complex with E3 ubiquitin ligase activity that interacts transiently with the CNOT1 subunit. Here, we attempt to investigate the role of human CNOT4 subunit in the DDR in human cells. MATERIAL AND METHODS: In this study, cell viability in the absence of CNOT4 was assessed using a Cell Titer-Glo Luminescence assay up to 4 days post siRNA transfection. In a further experiment, CNOT4-depleted HeLa cells were exposed to 3Gy ionizing radiation (IR). Ataxia telangiectasia-mutated (ATM) and ATM Rad3-related (ATR) signaling pathways were then investigated by western blotting for phosphorylated substrates. In addition, foci formation of histone 2A family member X (γH2AX), replication protein A (RPA), TP53 binding protein 1 (53BP1), and DNA repair protein RAD51 homolog 1 was also determined by immunofluorescence microscopy comparing control and CNOT4-depleted HeLa cells 0, 8, and 24 h post IR treatment. RESULTS: Our results from cell viability assays showed a significant reduction of cell growth activity at 24 (P value 0.02) and 48 h (P value 0.002) post siRNA. Western blot analysis showed slightly reduced or slightly delayed DDR signaling in CNOT4-depleted HeLa cells after IR. More significantly, we observed increased formation of γH2AX, RPA, 53BP1, and RAD51 foci after IR in CNOT4-depleted cells compared with the control cells. CONCLUSION: We conclude that depletion of CNOT4 affects various aspects of the cellular response to DNA damage.


Assuntos
Proteínas de Ciclo Celular , Radiação Ionizante , Animais , Humanos , Células HeLa , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Dano ao DNA , Reparo do DNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fosforilação , Mamíferos/genética , Mamíferos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
6.
Appl Radiat Isot ; 208: 111283, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38484590

RESUMO

A retrospective analysis of occupational exposure to ionizing radiation from medical uses and industrial uses in the three provinces of Central China from 2000 to 2021 was conducted. The average annual effective dose in medical uses and industrial uses decreased from 2.042 mSv and 2.334 mSv in 2000-2002 to 0.476 mSv and 0.371 mSv in 2021 respectively; the fraction of monitored workers receiving annual dose not exceeding 1 mSv increased from 60.78% and 74.45% in 2000-2002 to 94.20% and 96.85% in 2021 respectively, while receiving annual doses exceeding 20 mSv declined from 1.35% and 1.91% in 2000-2002 to 0.18% and 0.03% in 2021 respectively. The average annual effective dose and NR20 in the period 2000-2021 were relatively high in professional public health institutions (0.955 mSv and 0.004) and hospitals (0.815 mSv and 0.004). In 2021, the average annual effective dose to monitored workers in different occupational categories in medical uses in the three provinces of Central China were in the range of 0.199-0.692 mSv, with interventional radiology received the highest dose and NR20 (0.692 mSv and 0.005); the average annual effective dose ranged from 0.161 to 0.493 mSv in industrial uses, with industrial radiography received the highest dose and NR20 (0.493 mSv and 0.001). Occupational exposure in medical uses and industrial uses declined obviously in Central China, and the groups receiving higher doses are the radiation workers working in hospitals and professional public health institutions, or engaged in interventional radiology, nuclear medicine and industrial radiography, warranting more effective radiation protection measures.


Assuntos
Exposição Ocupacional , Exposição à Radiação , Monitoramento de Radiação , Humanos , Doses de Radiação , Monitoramento de Radiação/métodos , Estudos Retrospectivos , Radiação Ionizante , Exposição Ocupacional/análise , China
7.
Phys Chem Chem Phys ; 26(11): 8879-8890, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38426309

RESUMO

Radiation therapy uses ionizing radiation to break chemical bonds in cancer cells, thereby causing DNA damage and leading to cell death. The therapeutic effectiveness can be further increased by making the tumor cells more sensitive to radiation. Here, we investigate the role of the initial halogen atom core hole on the photofragmentation dynamics of 2-bromo-5-iodo-4-nitroimidazole, a potential bifunctional radiosensitizer. Bromine and iodine atoms were included in the molecule to increase the photoionization cross-section of the radiosensitizer at higher photon energies. The fragmentation dynamics of the molecule was studied experimentally in the gas phase using photoelectron-photoion-photoion coincidence spectroscopy and computationally using Born-Oppenheimer molecular dynamics. We observed significant changes between shallow core (I 4d, Br 3d) and deep core (I 3d) ionization in fragment formation and their kinetic energies. Despite the fact, that the ions ejected after deep core ionization have higher kinetic energies, we show that in a cellular environment, the ion spread is not much larger, keeping the damage well-localized.


Assuntos
Iodo , Nitroimidazóis , Raios Ultravioleta , Fótons , Radiação Ionizante
8.
Int J Mol Sci ; 25(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38474163

RESUMO

This work presents an ecological, flexible 2D radiochromic dosimeter for measuring ionizing radiation in the kilogray dose range. Cotton woven fabric made of cellulose was volume-modified with nitrotetrazolium blue chloride as a radiation-sensitive compound. Its features include a color change during exposure from yellowish to purple-brown and flexibility that allows it to adapt to various shapes. It was found that (i) the dose response is up to ~80 kGy, (ii) it is independent of the dose rate for 1.1-73.1 kGy/min, (iii) it can be measured in 2D using a flatbed scanner, (iv) the acquired images can be filtered using a mean filter, which improves its dose resolution, (v) the dose resolution is -0.07 to -0.4 kGy for ~0.6 to ~75.7 kGy for filtered images, and (vi) two linear dose subranges can be distinguished: ~0.6 to ~7.6 kGy and ~9.9 to ~62.0 kGy. The dosimeter combined with flatbed scanner reading and data processing using dedicated software packages constitutes a comprehensive system for measuring dose distributions for objects with complex shapes.


Assuntos
Dosímetros de Radiação , Radiação Ionizante , Celulose , Radiometria/métodos
9.
Sci Rep ; 14(1): 6119, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480827

RESUMO

Non-invasive methods of detecting radiation exposure show promise to improve upon current approaches to biological dosimetry in ease, speed, and accuracy. Here we developed a pipeline that employs Fourier transform infrared (FTIR) spectroscopy in the mid-infrared spectrum to identify a signature of low dose ionizing radiation exposure in mouse ear pinnae over time. Mice exposed to 0.1 to 2 Gy total body irradiation were repeatedly measured by FTIR at the stratum corneum of the ear pinnae. We found significant discriminative power for all doses and time-points out to 90 days after exposure. Classification accuracy was maximized when testing 14 days after exposure (specificity > 0.9 with a sensitivity threshold of 0.9) and dropped by roughly 30% sensitivity at 90 days. Infrared frequencies point towards biological changes in DNA conformation, lipid oxidation and accumulation and shifts in protein secondary structure. Since only hundreds of samples were used to learn the highly discriminative signature, developing human-relevant diagnostic capabilities is likely feasible and this non-invasive procedure points toward rapid, non-invasive, and reagent-free biodosimetry applications at population scales.


Assuntos
Exposição à Radiação , Radiometria , Humanos , Camundongos , Animais , Espectroscopia de Infravermelho com Transformada de Fourier , Análise de Fourier , Radiometria/métodos , Proteínas , Radiação Ionizante , Exposição à Radiação/análise , Doses de Radiação
10.
Health Phys ; 126(5): 296-308, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38526248

RESUMO

ABSTRACT: It is now well accepted that the mechanisms induced by low-dose exposures to ionizing radiation (LDR) are different from those occurring after high-dose exposures. However, the downstream effects of these mechanisms are unclear as are the quantitative relationships between exposure, effect, harm, and risk. In this paper, we will discuss the mechanisms known to be important with an overall emphasis on how so-called "non-targeted effects" (NTE) communicate and coordinate responses to LDR. Targeted deposition of ionizing radiation energy in cells causing DNA damage is still regarded as the dominant trigger leading to all downstream events whether targeted or non-targeted. We regard this as an over-simplification dating back to formal target theory. It ignores that last 100 y of biological research into stress responses and signaling mechanisms in organisms exposed to toxic substances, including ionizing radiation. We will provide evidence for situations where energy deposition in cellular targets alone cannot be plausible as a mechanism for LDR effects. An example is where the energy deposition takes place in an organism not receiving the radiation dose. We will also discuss how effects after LDR depend more on dose rate and radiation quality rather than actual dose, which appears rather irrelevant. Finally, we will use recent evidence from studies of cataract and melanoma induction to suggest that after LDR, post-translational effects, such as protein misfolding or defects in energy metabolism or mitochondrial function, may dominate the etiology and progression of the disease. A focus on such novel pathways may open the way to successful prophylaxis and development of new biomarkers for better risk assessment after low dose exposures.


Assuntos
Catarata , Exposição à Radiação , Humanos , Dano ao DNA , Mitocôndrias , Radiação Ionizante , Exposição à Radiação/efeitos adversos
11.
Cells ; 13(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38534394

RESUMO

This review discusses the relationship between cellular senescence and radiation exposure. Given the wide range of ionizing radiation sources encountered by people in professional and medical spheres, as well as the influence of natural background radiation, the question of the effect of radiation on biological processes, particularly on aging processes, remains highly relevant. The parallel relationship between natural and radiation-induced cellular senescence reveals the common aspects underlying these processes. Based on recent scientific data, the key points of the effects of ionizing radiation on cellular processes associated with aging, such as genome instability, mitochondrial dysfunction, altered expression of miRNAs, epigenetic profile, and manifestation of the senescence-associated secretory phenotype (SASP), are discussed. Unraveling the molecular mechanisms of cellular senescence can make a valuable contribution to the understanding of the molecular genetic basis of age-associated diseases in the context of environmental exposure.


Assuntos
Envelhecimento , Senescência Celular , Humanos , Senescência Celular/genética , Células Cultivadas , Radiação Ionizante
12.
BMC Cancer ; 24(1): 298, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443829

RESUMO

BACKGROUND: The surge in the utilization of CT scans for COVID-19 diagnosis and monitoring during the pandemic is undeniable. This increase has brought to the forefront concerns about the potential long-term health consequences, especially radiation-induced cancer risk. This study aimed to quantify the potential cancer risk associated with CT scans performed for COVID-19 detection. METHODS: In this cross-sectional study data from a total of 561 patients, who were referred to the radiology center at Imam Hossein Hospital in Shahroud, was collected. CT scan reports were categorized into three groups based on the radiologist's interpretation. The BEIR VII model was employed to estimate the risk of radiation-induced cancer. RESULTS: Among the 561 patients, 299 (53.3%) were males and the average age of the patients was 49.61 ± 18.73 years. Of the CT scans, 408 (72.7%) were reported as normal. The average age of patients with normal, abnormal, and potentially abnormal CT scans was 47.57 ± 19.06, 54.80 ± 16.70, and 58.14 ± 16.60 years, respectively (p-value < 0.001). The average effective dose was 1.89 ± 0.21 mSv, with 1.76 ± 0.11 mSv for males and 2.05 ± 0.29 mSv for females (p-value < 0.001). The average risk of lung cancer was 3.84 ± 1.19 and 9.73 ± 3.27 cases per 100,000 patients for males and females, respectively. The average LAR for all cancer types was 10.30 ± 6.03 cases per 100,000 patients. CONCLUSIONS: This study highlights the critical issue of increased CT scan usage for COVID-19 diagnosis and the potential long-term consequences, especially the risk of cancer incidence. Healthcare policies should be prepared to address this potential rise in cancer incidence and the utilization of CT scans should be restricted to cases where laboratory tests are not readily available or when clinical symptoms are severe.


Assuntos
COVID-19 , Neoplasias Induzidas por Radiação , Feminino , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Teste para COVID-19 , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , COVID-19/epidemiologia , Tomografia Computadorizada por Raios X/efeitos adversos , Radiação Ionizante
13.
Artigo em Inglês | MEDLINE | ID: mdl-38432778

RESUMO

The dosimetry and control of exposure for individuals chronically exposed to ionizing radiation are important and complex issues. Assessment may be optimized by evaluating individual adaptation and radiosensitivity, but it is not possible for a single model to account for all relevant parameters. Our goal was to develop approaches for the calculation of doses for persons chronically exposed to ionizing radiation, taking their radiosensitivities into consideration. On the basis of ex vivo radiation of blood samples, dose-effect models were constructed for dose ranges 0.01-2.0 and 0.01-0.4 Gy, using different cytogenetic criteria. The frequencies of "dicentric chromosomes and rings" at low doses are too low to have predictive value. The different responses of subjects to radiation made it possible to categorize them according to their radiosensitivities and to generate separate dose-effect curves for radiosensitive, average, and radioresistant individuals, reducing the amount of error in retrospective dosimetry.


Assuntos
Tolerância a Radiação , Radiação Ionizante , Humanos , Estudos Retrospectivos , Citogenética , Tolerância a Radiação/genética , Análise Citogenética
14.
Sci Total Environ ; 924: 171567, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38460702

RESUMO

In nature, plants are simultaneously exposed to different abiotic (e.g., heat, drought, and salinity) and biotic (e.g., bacteria, fungi, and insects) stresses. Climate change and anthropogenic pressure are expected to intensify the frequency of stress factors. Although plants are well equipped with unique and common defense systems protecting against stressors, they may compromise their growth and development for survival in such challenging environments. Ionizing radiation is a peculiar stress factor capable of causing clustered damage. Radionuclides are both naturally present on the planet and produced by human activities. Natural and artificial radioactivity affects plants on molecular, biochemical, cellular, physiological, populational, and transgenerational levels. Moreover, the fitness of pests, pathogens, and symbionts is concomitantly challenged in radiologically contaminated areas. Plant responses to artificial acute ionizing radiation exposure and laboratory-simulated or field chronic exposure are often discordant. Acute or chronic ionizing radiation exposure may occasionally prime the defense system of plants to better tolerate the biotic stress or could often exhaust their metabolic reserves, making plants more susceptible to pests and pathogens. Currently, these alternatives are only marginally explored. Our review summarizes the available literature on the responses of host plants, biotic factors, and their interaction to ionizing radiation exposure. Such systematic analysis contributes to improved risk assessment in radiologically contaminated areas.


Assuntos
Plantas , Radioatividade , Animais , Humanos , Radiação Ionizante , Estresse Fisiológico , Insetos
15.
Food Funct ; 15(7): 3522-3538, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38465872

RESUMO

The numerous beneficial probiotic properties of Lactobacillus reuteri (L. reuteri) include decreasing metabolic syndrome, preventing disorders linked to oxidative stress, improving gut flora imbalances, controlling immunological function, and extending life span. Exposure to ionizing radiation is closely associated with several disorders. We examined the protective and salvaging effects of L. reuteri on ionizing radiation-induced injury to the intestinal tract, reproductive system, and nervous system of Drosophila melanogaster. We also examined its effects on lifespan, antioxidant capacity, progeny development, and behavioral aspects to assess the interaction between L. reuteri and ionizing radiation-induced injury. The findings demonstrated that L. reuteri improved the median survival time following irradiation and greatly extended its lifespan. In addition, it raised SOD activity, reduced ROS levels in intestinal epithelial cells, and increased the quantity of intestinal stem cells. Furthermore, L. reuteri enhanced the adult male flies' capacity to move. It also successfully safeguarded the generations' growth and development. L. reuteri dramatically enhanced expression of the AMPKα gene and regulated expression of its pathway-related gene, mTOR, as well as the autophagy-related genes Atg1 and Atg5 in female Drosophila exposed to irradiation. Notably, no prior reports have been made on the possible effects of L. reuteri on injuries caused by irradiation. As a result, our research offers important new information regarding L. reuteri's possible role as a shield against ionizing radiation-induced injury.


Assuntos
Limosilactobacillus reuteri , Probióticos , Animais , Masculino , Feminino , Lactobacillus , Drosophila melanogaster , Intestinos , Radiação Ionizante , Probióticos/farmacologia
17.
Radiat Res ; 201(4): 275-286, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38453644

RESUMO

We present an extension of the Local Effect Model (LEM) to include time-dose relationships for predicting effects of protracted and split-dose ion irradiation at arbitrary LET. With this kinetic extension, the spatial and temporal induction and processing of DNA double strand breaks (DSB) in cellular nuclei can be simulated for a wide range of ion radiation qualities, doses and dose rates. The key concept of the extension is based on the joint spatial and temporal coexistence of initial DSB, leading to the formation of clustered DNA damage on the µm scale (as defined e.g., by the size scale of Mbp chromatin loops), which is considered to have an increased cellular lethality as compared to isolated, single DSB. By simulating the time dependent induction and repair of DSB and scoring of isolated and clustered DSB upon irradiation, the impact of dose rate and split dose on the cell survival probability can be computed. In a first part of this work, we systematically analyze the predicted impact of protraction in dependence of factors like dose, LET, ion species and radiosensitivity as characterized by the photon LQ-parameters. We establish links to common concepts that describe dose rate effects for low LET radiation. We also compare the model predictions to experimental data and find agreement with the general trends observed in the experiments. The relevant concepts of our approach are compared to other models suitable for predicting time effects. We investigate an apparent analogy between spatial and temporal concentration of radiation delivery, both leading to increased effectiveness, and discuss similarities and differences between the general dependencies of these clustering effects on their impacting factors. Finally, we conclude that the findings give additional support for the general concept of the LEM, i.e. the characterization of high LET radiation effects based on the distinction of just two classes of DSB (isolated DSB and clustered DSB).


Assuntos
Quebras de DNA de Cadeia Dupla , Radiação Ionizante , Dano ao DNA , Núcleo Celular , Sobrevivência Celular/efeitos da radiação , Reparo do DNA
18.
Biochim Biophys Acta Mol Basis Dis ; 1870(4): 167062, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342416

RESUMO

Primary cilia are antenna-like organelles that play critical roles in sensing and responding to various signals. Nevertheless, the function of primary cilia in cellular response to ionizing radiation (IR) in tumor cells remains unclear. Here, we show that primary cilia are frequently expressed in tumor cells and tissues. Notably, IR promotes cilia formation and elongation in time- and dose-dependent manners. Mechanistic study shows that the suppression of YAP/Aurora A pathway contributes to IR-induced ciliogenesis, which is diminished by Aurora A overexpression. The ciliated tumor cells undergo senescence but not apoptosis in response to IR and the abrogation of cilia formation is sufficient to elevate the lethal effect of IR. Furthermore, we show that IR-induced ciliogenesis leads to the activation of Hedgehog signaling pathway to drive senescence and resist apoptosis, and its blockage enhances cellular radiosensitivity by switching senescence to apoptosis. In summary, this work shows evidence of primary cilia in coordinating cellular response to IR in tumor cells, which may help to supply a novel sensitizing target to improve the outcome of radiotherapy.


Assuntos
Cílios , Proteínas Hedgehog , Apoptose , Cílios/metabolismo , Proteínas Hedgehog/metabolismo , Radiação Ionizante , Transdução de Sinais , Humanos
19.
Clin Epigenetics ; 16(1): 19, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38303056

RESUMO

BACKGROUND: Environmental exposure, medical diagnostic and therapeutic applications, and industrial utilization of radionuclides have prompted a growing focus on the risks associated with low-dose radiation (< 100 mGy). Current evidence suggests that such radiation can induce epigenetic changes. Nevertheless, whether exposure to low-dose radiation can disrupt endothelial cell function at the molecular level is unclear. Because endothelial cells play crucial roles in cardiovascular health and disease, we aimed to investigate whether low-dose radiation could lead to differential DNA methylation patterns at the genomic level in endothelial cell (EC) lines. METHODS: We screened for changes in DNA methylation patterns in primary human aortic (HAECs) and coronary artery endothelial cells following exposure to low-dose ionizing radiation. Using a subset of genes altered via DNA methylation by low-dose irradiation, we performed gene ontology (GO) analysis to predict the possible biological network mediating the effect of low-dose radiation. In addition, we performed comprehensive validation using methylation and gene expression analyses, and ChIP assay to identify useful biomarkers among candidate genes for use in detecting low-dose radiation exposure in human primary normal ECs. RESULTS: Low-dose radiation is sufficient to induce global DNA methylation alterations in normal EC lines. GO analysis demonstrated that these hyper- or hypo-methylated genes were linked to diverse biological pathways. Our findings indicated a robust correlation between promoter hypermethylation and transcriptional downregulation of four genes (PGRMC1, UNC119B, RERE, and FNDC3B) in response to low-dose ionizing radiation in HAECs. CONCLUSIONS: Based on these findings, the identified genes can serve as potential DNA methylation biomarkers for the assessment of cardiovascular risk upon exposure to low-dose radiation.


Assuntos
Doenças Cardiovasculares , Metilação de DNA , Humanos , Epigenoma , Células Endoteliais , Doenças Cardiovasculares/genética , Biomarcadores , Radiação Ionizante , Proteínas de Membrana/genética , Receptores de Progesterona/genética
20.
Drug Dev Ind Pharm ; 50(3): 262-273, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38334353

RESUMO

OBJECTIVE: The present study aimed to assess the radioprotective effect of nanoniosomes loaded by Mentha Pulegium essential oil (MPEO-N nanoparticles) as a natural antioxidant on human peripheral blood mononuclear cells (PBMCs). SIGNIFICANCE: Despite the applications and advantages of ionizing radiation, there are many radiation risks to biological systems that are necessary to be reduced as much as possible. METHODS: MPEO-N nanoparticles were prepared by the lipid thin film hydration method, and its physicochemical characteristics were analyzed. PBMCs were then irradiated with X-ray using a 6 MV linear accelerator at two radiation doses in the presence of nontoxic concentrations of MPEO-N nanoparticles (IC10). After 48 and 72 h of incubation, the radioprotective effect was investigated by measuring survival, apoptosis, and necrosis of PBMCs, using MTT assay and flow cytometry analysis. KEY FINDINGS: The hydrodynamic diameter and zeta potential of nanoniosomes were 106.0 ± 4.69 nm and -15.2 ± 0.9 mV, respectively. The mean survival percentage of PBMCs showed a significant increase only at a radiation dose of 200 cGy compared with the control group. The percentages of apoptosis and necrosis of cells in the presence of MPEO-N nanoparticles at both radiation doses and incubation periods (48 and 72 h) demonstrated a significant reduction compared with the control. CONCLUSION: MPEO-N nanoparticles as a natural antioxidant, exhibited a favorable radioprotective effect by a significant reduction in the percentage of apoptosis and necrosis of irradiated PBMCs.


Assuntos
Mentha pulegium , Óleos Voláteis , Humanos , Óleos Voláteis/farmacologia , Antioxidantes/farmacologia , Leucócitos Mononucleares , Radiação Ionizante , Necrose
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