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1.
J Radiol Prot ; 44(2)2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38569480

ABSTRACT

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.


Subject(s)
Occupational Exposure , Radiation Protection , Humans , Health Knowledge, Attitudes, Practice , Health Personnel , Radiometry , Radiation, Ionizing , Hospitals , Occupational Exposure/prevention & control , Occupational Exposure/analysis
2.
Sci Rep ; 14(1): 8468, 2024 04 11.
Article in English | MEDLINE | ID: mdl-38605022

ABSTRACT

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.


Subject(s)
Proton Therapy , Radiation Injuries , Humans , Proton Therapy/methods , Protons , Radiation, Ionizing , Monte Carlo Method , Etoposide , Dose Fractionation, Radiation , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted
3.
Sud Med Ekspert ; 67(2): 39-42, 2024.
Article in Russian | MEDLINE | ID: mdl-38587157

ABSTRACT

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.


Subject(s)
Radiation, Ionizing , Retrospective Studies
4.
Article in English | MEDLINE | ID: mdl-38432778

ABSTRACT

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.


Subject(s)
Radiation Tolerance , Radiation, Ionizing , Humans , Retrospective Studies , Cytogenetics , Radiation Tolerance/genetics , Cytogenetic Analysis
5.
Int J Mol Sci ; 25(5)2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38474163

ABSTRACT

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.


Subject(s)
Radiation Dosimeters , Radiation, Ionizing , Cellulose , Radiometry/methods
6.
Cell Cycle ; 23(3): 233-247, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38551450

ABSTRACT

Colorectal cancer (CRC) poses a significant challenge in terms of treatment due to the prevalence of radiotherapy resistance. However, the underlying mechanisms responsible for radio-resistance in CRC have not been thoroughly explored. This study aimed to shed light on the role of human coilin interacting nuclear ATPase protein (hCINAP) in radiation-resistant HT-29 and SW480 CRC cells (HT-29-IR and SW480-IR) and investigate its potential implications. Firstly, radiation-resistant CRC cell lines were established by subjecting HT-29 and SW480 cells to sequential radiation exposure. Subsequent analysis revealed a notable increase in hCINAP expression in radiation-resistant CRC cells. To elucidate the functional role of hCINAP in radio-resistance, knockdown experiments were conducted. Remarkably, knockdown of hCINAP resulted in an elevation of reactive oxygen species (ROS) generation upon radiation treatment and subsequent activation of apoptosis mediated by mitochondria. These observations indicate that hCINAP depletion enhances the radiosensitivity of CRC cells. Conversely, when hCINAP was overexpressed, it was found to enhance the radio-resistance of CRC cells. This suggests that elevated hCINAP expression contributes to the development of radio-resistance. Further investigation revealed an interaction between hCINAP and ATPase family AAA domain containing 3A (ATAD3A). Importantly, ATAD3A was identified as an essential factor in hCINAP-mediated radio-resistance. These findings establish the involvement of hCINAP and its interaction with ATAD3A in the regulation of radio-resistance in CRC cells. Overall, the results of this study demonstrate that upregulating hCINAP expression may improve the survival of radiation-exposed CRC cells. Understanding the intricate molecular mechanisms underlying hCINAP function holds promise for potential strategies in targeted radiation therapy for CRC. These findings emphasize the importance of further research to gain a comprehensive understanding of hCINAP's precise molecular mechanisms and explore its potential as a therapeutic target in overcoming radio-resistance in CRC. By unraveling the complexities of hCINAP and its interactions, novel therapeutic approaches may be developed to enhance the efficacy of radiation therapy and improve outcomes for CRC patients.


Subject(s)
ATPases Associated with Diverse Cellular Activities , Apoptosis , Colorectal Neoplasms , Gene Knockdown Techniques , Radiation Tolerance , Reactive Oxygen Species , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/radiotherapy , Radiation Tolerance/genetics , Apoptosis/radiation effects , Apoptosis/genetics , Reactive Oxygen Species/metabolism , ATPases Associated with Diverse Cellular Activities/metabolism , ATPases Associated with Diverse Cellular Activities/genetics , Cell Line, Tumor , Radiation, Ionizing , Mitochondria/metabolism , Mitochondria/radiation effects , HT29 Cells
7.
Radiat Res ; 201(4): 275-286, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38453644

ABSTRACT

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).


Subject(s)
DNA Breaks, Double-Stranded , Radiation, Ionizing , DNA Damage , Cell Nucleus , Cell Survival/radiation effects , DNA Repair
8.
Appl Radiat Isot ; 208: 111283, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38484590

ABSTRACT

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.


Subject(s)
Occupational Exposure , Radiation Exposure , Radiation Monitoring , Humans , Radiation Dosage , Radiation Monitoring/methods , Retrospective Studies , Radiation, Ionizing , Occupational Exposure/analysis , China
9.
J Cancer Res Ther ; 20(1): 126-132, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38554309

ABSTRACT

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.


Subject(s)
Cell Cycle Proteins , Radiation, Ionizing , Animals , Humans , HeLa Cells , Ataxia Telangiectasia Mutated Proteins/genetics , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , DNA Damage , DNA Repair , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Phosphorylation , Mammals/genetics , Mammals/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
10.
Cells ; 13(6)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38534394

ABSTRACT

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.


Subject(s)
Aging , Cellular Senescence , Humans , Cellular Senescence/genetics , Cells, Cultured , Radiation, Ionizing
12.
Sci Total Environ ; 924: 171567, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38460702

ABSTRACT

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.


Subject(s)
Plants , Radioactivity , Animals , Humans , Radiation, Ionizing , Stress, Physiological , Insecta
13.
Food Funct ; 15(7): 3522-3538, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38465872

ABSTRACT

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.


Subject(s)
Limosilactobacillus reuteri , Probiotics , Animals , Male , Female , Lactobacillus , Drosophila melanogaster , Intestines , Radiation, Ionizing , Probiotics/pharmacology
14.
Radiother Oncol ; 194: 110198, 2024 May.
Article in English | MEDLINE | ID: mdl-38438016

ABSTRACT

BACKGROUND AND PURPOSE: Ionizing radiation (IR) induces DNA double-strand breaks (DSBs), leading to micronuclei formation, which has emerged as a key mediator of inflammatory responses after IR. This study aimed to investigate the signaling cascade in inflammatory gene expression using fibroblasts harboring DNA damage response deficiency after exposure to IR. MATERIALS AND METHODS: Micronuclei formation was examined in human dermal fibroblasts derived from patients with deficiencies in ATM, ATR, MRE11, XLF, Artemis, or BRCA2 after IR. RNA-sequencing analysis was performed to assess gene expression, pathway mapping, and the balance of transcriptional activity using the transcription factor-based downstream gene expression mapping (TDEM) method developed in this study. RESULTS: Deficiencies in ATM, ATR, or MRE11 led to increased micronuclei formation after IR compared to normal cells. RNA-seq analysis revealed significant upregulation of inflammatory expression in cells deficient in ATM, ATR, or MRE11 following IR. Pathway mapping analysis identified the upregulation of RIG-I, MDA-5, IRF7, IL6, and interferon stimulated gene expression after IR. These changes were pronounced in cells deficient in ATM, ATR, or MRE11. TDEM analysis suggested the differential activation of STAT1/3-pathway between ATM and ATR deficiency. CONCLUSION: Enhanced micronuclei formation upon ATM, ATR, or MRE11 deficiency activated the cGAS/STING, RIG-I-MDA-5-IRF7-IL6 pathway, resulting in its downstream interferon stimulated gene expression following exposure to IR. Our study provides comprehensive information regarding the status of inflammation-related gene expression under DSB repair deficiency after IR. The generated dataset may be useful in developing functional biomarkers to accurately identify patients sensitive to radiotherapy.


Subject(s)
Ataxia Telangiectasia Mutated Proteins , Fibroblasts , Radiation, Ionizing , Signal Transduction , Humans , Fibroblasts/radiation effects , Fibroblasts/metabolism , Ataxia Telangiectasia Mutated Proteins/genetics , Ataxia Telangiectasia Mutated Proteins/deficiency , Ataxia Telangiectasia Mutated Proteins/metabolism , MRE11 Homologue Protein/genetics , Inflammation/etiology , DNA Breaks, Double-Stranded
15.
Rev Bras Epidemiol ; 27: e240011, 2024.
Article in English, Portuguese | MEDLINE | ID: mdl-38511821

ABSTRACT

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.


Subject(s)
Neoplasms , Occupational Diseases , Occupational Exposure , Humans , Cohort Studies , Retrospective Studies , Brazil/epidemiology , Radiation, Ionizing , Occupational Exposure/adverse effects , Occupational Diseases/etiology
16.
Sci Rep ; 14(1): 6119, 2024 03 13.
Article in English | MEDLINE | ID: mdl-38480827

ABSTRACT

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.


Subject(s)
Radiation Exposure , Radiometry , Humans , Mice , Animals , Spectroscopy, Fourier Transform Infrared , Fourier Analysis , Radiometry/methods , Proteins , Radiation, Ionizing , Radiation Exposure/analysis , Radiation Dosage
17.
Health Phys ; 126(5): 296-308, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38526248

ABSTRACT

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.


Subject(s)
Cataract , Radiation Exposure , Humans , DNA Damage , Mitochondria , Radiation, Ionizing , Radiation Exposure/adverse effects
18.
Phys Chem Chem Phys ; 26(11): 8879-8890, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38426309

ABSTRACT

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.


Subject(s)
Iodine , Nitroimidazoles , Ultraviolet Rays , Photons , Radiation, Ionizing
19.
BMC Cancer ; 24(1): 298, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38443829

ABSTRACT

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.


Subject(s)
COVID-19 , Neoplasms, Radiation-Induced , Female , Male , Humans , Adult , Middle Aged , Aged , Cross-Sectional Studies , COVID-19 Testing , Neoplasms, Radiation-Induced/diagnosis , Neoplasms, Radiation-Induced/epidemiology , Neoplasms, Radiation-Induced/etiology , COVID-19/epidemiology , Tomography, X-Ray Computed/adverse effects , Radiation, Ionizing
20.
Ecotoxicol Environ Saf ; 273: 116128, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38387144

ABSTRACT

BACKGROUND: Low-dose ionizing radiation-induced protection and damage are of great significance among radiation workers. We aimed to study the role of glutathione S-transferase Pi (GSTP1) in low-dose ionizing radiation damage and clarify the impact of ionizing radiation on the biological activities of cells. RESULTS: In this study, we collected peripheral blood samples from healthy adults and workers engaged in radiation and radiotherapy and detected the expression of GSTP1 by qPCR. We utilized γ-rays emitted from uranium tailings as a radiation source, with a dose rate of 14 µGy/h. GM12878 cells subjected to this radiation for 7, 14, 21, and 28 days received total doses of 2.4, 4.7, 7.1, and 9.4 mGy, respectively. Subsequent analyses, including flow cytometry, MTS, and other assays, were performed to assess the ionizing radiation's effects on cellular biological functions. In peripheral blood samples collected from healthy adults and radiologic technologist working in a hospital, we observed a decreased expression of GSTP1 mRNA in radiation personnel compared to the healthy controls. In cultured GM12878 cells exposed to low-dose ionizing radiation from uranium tailings, we noted significant changes in cell morphology, suppression of proliferation, delay in cell cycle progression, and increased apoptosis. These effects were partially reversed by overexpression of GSTP1. Moreover, low-dose ionizing radiation increased GSTP1 gene methylation and downregulated GSTP1 expression. Furthermore, low-dose ionizing radiation affected the expression of GSTP1-related signaling molecules. CONCLUSIONS: This study shows that low-dose ionizing radiation damages GM12878 cells and affects their proliferation, cell cycle progression, and apoptosis. In addition, GSTP1 plays a modulating role under low-dose ionizing radiation damage conditions. Low-dose ionizing radiation affects the expression of Nrf2, JNK, and other signaling molecules through GSTP1.


Subject(s)
Glutathione S-Transferase pi , Uranium , Adult , Humans , Glutathione S-Transferase pi/genetics , Radiation, Ionizing , Gamma Rays/adverse effects , Apoptosis
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