International journal of radiation biology最新文献

Purpose: Tumor hypoxia is a negative prognostic factor that causes radiotherapy resistance. Decades of clinical trials employing various hypoxia intervention strategies have had limited impact on daily clinical practise. This is largely due to modest benefits of hypoxia modification in unselected patient populations, combined with higher toxicity and increases in cost and time. However, numerous studies have employed post-hoc analysis to demonstrate a benefit of hypoxia intervention in patients with the most hypoxic tumors, and these benefits are of sufficient magnitude to warrant further pursuit. For the first time, we have recently seen the emergence of interventional trials with patient selection or stratification based on tumor hypoxia biomarkers. The purpose of this mini-review is to present the design and results from these recent trials, and highlight their impact in propelling this field forward.

Conclusions: Recent trials employing patient selection based on hypoxia biomarkers have investigated the effects of dose (distribution) modifications, and drug-induced tumor reoxygenation or radiosensitization. Encouraging results from some approaches have laid the foundation for larger follow-up studies that have the potential to change clinical practice. These clinical trials set an important precedent for future trial design and help guide the path for the future of hypoxia-directed radiotherapy.

Purpose: The dicentric chromosome assay (DCA), recognized as the gold standard for biological dosimetry in emergency radiation exposure, involves multiple key steps. Among these, metaphase image selection remains ambiguous and particularly challenging for beginners. This study evaluates the impact of metaphase image selection on dicentric (Dic) frequency during initial training.

Materials and methods: Peripheral blood (PB) from three healthy donors was irradiated with 2 Gy X-rays and incubated at 37 °C for 2 h for DNA repair. PB samples were then cultured for 48 h with phytohemagglutinin and colcemid. After fixation, metaphase spreads were prepared, Giemsa-stained, and images were captured by specific microscope imaging and image processing software. Three beginners independently selected and analyzed 50 metaphase images each. A trainer with experience in performing radiation emergency related DCA then reviewed and removed unsuitable images. The beginners reanalyzed Dic frequencies, supplementing with additional images as needed to reach 50 metaphases. Dic frequencies were compared before and after image refinement.

Results: Dic frequencies were lower in metaphase image pools selected by beginners compared to those refined by the trainer. The novices' selections included numerous over-condensed metaphases, making Dic detection difficult.

Conclusion: Blood culture for 48 h permanent colcemid treatment increases the occurrence of over-condensed chromosomes, affecting Dic scoring. This study highlights the importance of proper training in metaphase image selection and structured education on quality assessment, including the use of specific microscope imaging and image processing software to ensure accurate biological dosimetry.

Introduction: Although the dosimetry technique using fingernails coupled with electron paramagnetic/spin resonance (EPR/ESR) spectroscopy (hereafter called 'fingernail EPR dosimetry') has practical advantages, more efforts to improve its accuracy and reliability are required for application to dose assessment in radiological accidents.

Purpose: In fingernail EPR dosimetry, an absorbed dose is determined from the peak-to-peak amplitude of the main peak of the EPR signal spectrum, whereas the measured spectrum is the first derivative of the microwave absorption band. This study aimed to confirm the validity of this approach based on peak deconvolution analysis of the integrated EPR spectra of irradiated fingernails.

Methods: Fingernail samples collected from two donors (an 11-year-old child and a 62-year-old adult) were irradiated with X-rays (160 kV, 6.3 mA) at different doses (0, 5, 10, and 20 Gy) and EPR signals were measured using an X-band EPR spectrometer. The measured EPR spectra were integrated and deconvoluted into major components.

Results: The integrated EPR spectra were successfully deconvoluted into three Gaussian peaks with central magnetic field values of 327.42, 327.55, and 327.63 mT. All the peaks of the child fingernails showed linear dose responses. In contrast, the three peaks of the adult fingernails presented notably different dose responses; it was implied that the reduction in radiation sensitivity of the peak-to-peak amplitude was not attributable to the major peak.

Conclusions: The findings presented in this study underscore the importance of examining the behaviors of the overlapping peaks in fingernail EPR spectra on an individual basis to achieve more reliable fingernail EPR dosimetry.

Purpose: Dosimetry technique using fingernails coupled with electron paramagnetic/spin resonance (EPR or ESR) spectroscopy has gained attention for its potential in radiation dose assessment. This technique detects radiation-induced signals (RIS) within keratin in fingernail; however, variations in background signals (BGS) complicate dose assessments. This study aimed to improve the accuracy of fingernail dosimetry and further develop universal protocols by systematically analyzing BGS intensities in relation to donor ages.

Materials and methods: Fingernail samples collected from 12 donors of different ages (11-64 years) were analyzed using an X-band ESR spectrometer before and after water treatment. Selected samples were irradiated with X-rays (160 kV, 6.3 mA) at 5 Gy and 10 Gy, then treated and measured to examine the BGS and RIS intensities.

Results: Water treatment significantly reduced BGS intensities of all fingernail samples, decreasing the intra-individual variation from 1.2-8% to 0.2-2.8% and the inter-individual variation from 94% to 36%. A declining trend of post-water-treatment BGS intensity with age was observed, with a notable difference between children and adults. The BGS of toenails showed characteristics similar to those of fingernails. The post-treatment BGS intensities in the irradiated samples were slightly higher than those in the unirradiated ones.

Conclusion: This study presented a large variability in the initial BGS intensities of fingernails between children and adults and the potential of toenails as a control sample in fingernail dosimetry. These findings highlight the importance of further comprehensive studies on individual-based fingernail dosimetry and its universal protocols.

Purpose: The number of oxygen vacancies in quartz measured by electron spin resonance (ESR) as the intensity of the E₁' center has been used to investigate the provenance of the sediments and has been found to be a good proxy in discussing the direction and intensity of the wind system in the past. While its temporal variations have been examined using marine sediments. The present study aimed to show that terrestrial sediments are also useful for such studies on climate change when it is continuous.

Materials and methods: Samples from a continuous tephric loess sequence were examined in the present study. Samples were collected from Kamiyoshida outcrop in Rokunohe Town, Aomori Prefecture, with 5 cm intervals from 110 cm to 420 cm, and a total of 61 samples were analyzed. XRD (X-ray diffraction) analysis was employed to correct the content of quartz in the chemically processed samples.

Results and conclusions: Three peaks of the number of oxygen vacancies were observed (15-20, 40-50, and 70-75 ka) for the grain size fractions <2-20, and 20-50 µm. These three peeks look corresponding to the peaks in marine sediments observed in a previous work. During these periods, the amount of eolian dust supplied from the Chinese continent may have been larger, resulting in higher oxygen vacancy values in quartz in both sediments of Sea of Japan and of tephric loess sequence on land. The present results indicate that land sedimentary sequence would be as useful as marine sediments for studying past wind systems.

Purpose: Radiation-induced fibrosis (RIF) is a significant long-term complication of radiotherapy, affecting many cancer patients months to years after treatment. Characterized by progressive tissue stiffening, loss of elasticity, and impaired organ function, RIF can deleteriously impact a patient's quality of life. Commonly affected sites include the skin, lung, heart, and kidney. Advances in radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), stereotactic body radiotherapy (SBRT), and image-guided radiotherapy (IGRT), have improved the precision of radiation delivery, reducing acute damage to healthy tissues; RIF however, remains a prevalent complication despite these technological advancements. This review explores the underlying cellular and molecular mechanisms of RIF, emphasizing fibroblast proliferation, myofibroblast activation, and excessive extracellular matrix (ECM) deposition in its progression. Additionally, this review highlights in vitro and in vivo models that are instrumental in studying RIF and evaluates current therapeutic strategies aimed at mitigating RIF.

Conclusion: Radiation-induced fibrosis continues to affect a considerable number of patients due to the chronic nature of the fibrotic processes, driven by sustained fibroblast activation, ECM accumulation, and inflammatory responses. Newly developed approaches, such as stem cell-based therapies, TGF-β inhibitors, and molecular interventions aimed at ECM regulation, offer promising avenues for mitigating or reversing RIF. Additionally, integrating computational models into clinical practice could enhance personalized treatment planning, enabling better prediction and prevention of RIF in patients. Addressing these challenges is critical for improving the quality of life of patients affected by RIF and improving their outcomes, particularly with the growing population of long-term cancer survivors in the world.

Purpose: In case of an accidental or malevolent radiological event involving a large number of potential victims, fast and correct classification in terms of level of exposure is of utmost importance, not only for those that require specific medical treatment, but also for those that were not exposed. Our goal was to develop a system allowing to classify as many potential victims as possible in our laboratory by using the reference cytogenetic biodosimetry assay.

Materials and methods: A system was created with a theoretical classification of 320 individuals 13 days after sample reception by using a triage-mode dicentric chromosome assay (DCA). After preliminary tests to verify the system logistics and equipment, a partial-capacity exercise was performed, where 120 blood samples were irradiated with 6 MV X-rays at doses ranging from 0 to 4.5 Gy. Operators were asked to treat and analyze the blindly coded samples by applying specific protocols and to respect an established deadline.

Results: Deployment of the system was successful and pre-planned logistics were applied as instructed. Classification results were compiled with a strict time limit and following previous developments, 3 radiation exposure grading scales of 5, 4 and 3 classes were applied. Correct classification ranged from 85 to 92%, depending on the grading scale used.

Conclusions: This partial-capacity exercise contributed to validate the newly developed organizational system, showing promising results. Points of improvement were clearly identified, and current efforts are focused toward maximizing the correct classification percentage and testing the maximal capacity of the system.

Purpose: Phosphorylation of the histone H2AX (γ-H2AX) is a rapid response to radiation-induced DNA double strand breaks (DSBs) and is a good biomarker for exposure to ionizing radiation. The signal has traditionally been detected by microscopy (spot counting) or by flow cytometry (fluorescent intensity). An imaging flow cytometry (IFC) method has been developed, which combines the high resolution of microscopy with the statistical power of flow cytometry methods to measure γ-H2AX in human lymphocytes.

Materials and methods: The assay was optimized and validated for both sample acquisition and data analysis, in the dose range of 0-10 Gy. For data analysis, mean fluorescence intensity (MFI), spot count (foci per cell), and average area of the spots were used with the supervised machine learning (SML) K-Nearest Neighbors (K-NN) algorithm to estimate doses. These dose estimates were compared to the traditional flow cytometry method of estimating doses from an MFI-based dose response curve.

Results: A statistical analysis of both methodologies showed that SML K-NN method was able to determine the dose delivered to blind, irradiated samples more accurately than when using a linear fit of the MFI response alone, especially in the 7-10 Gy dose range.

Conclusions: The efficiency of the γ-H2AX-IFC assay, 1 hour post-exposure, has been improved and validated using the SML K-NN methodology for dose estimation. This study could help establish the γ-H2AX assay as a triage tool for the rapid screening of a large number of samples.

Purpose: To apply electron spin resonance (ESR) dosimetry to wild Japanese macaques captured in the ex-evacuation area during the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, the improvement of the detection limit is crucial. In this study, we optimized the microwave power in ESR measurements to suppress the noise of native radicals and enhanced the signals of radiation-induced carbonate radicals.

Materials and methods: Tooth enamels of a Japanese macaque captured in a control area were prepared and irradiated with gamma rays from ⁶⁰Co source. The ESR spectra of the enamel samples with different absorbed doses ranging from 0 to 1800 mGy were measured with varying microwave power. The ESR spectra were analyzed by an in-house multi-component decomposition code using a simulated annealing method.

Results: Intensities of both components originating from carbonate and native radicals saturated and decayed as the microwave power increased. The intensity ratio of carbonate radicals to native radicals, i.e., signal to noise ratio, increased monotonically at microwave powers below 30 mW. We also examined the linearity of the intensity of carbonate radicals against the absorbed doses and recommended a microwave power range of 5-25 mW.

Conclusion: In this study, we showed that optimizing the microwave power is an effective way to improve the quantitation accuracy of carbonate radicals in samples with low absorbed doses. The improved measurement conditions will expand the applicable range of ESR dosimetry for research on the effects of radiation on wild animals related to the FDNPP accident.

Purpose: This paper characterizes types of biodosimetric tools used for response and treatment in a large-scale nuclear event. Using US official documents to define dangerous zones and centers for triage and treatment, the types of biodosimetry needed in various circumstances, based on likely volumes, types of radiation and extent of combined injuries of people arriving at different center locations, are defined.

Conclusions: Appropriate biodosimetry methods should consider the type of radiation received (predominantly prompt mixed gamma-neutron irradiation or gamma rays from fallout), probability of physical injury/burns, the likelihood of receiving a significant dose, and the location and number of likely victims. The types of parameters needed for using biodosimetric techniques most effectively in a nuclear event, including for methods to be developed, are denoted for seven distinct situations that would occur with a large-scale nuclear event. The analysis leads to the conclusion that the benefit of using qualitative biodosimetry for stage 1 triage of people who were in dangerous zones is low and not recommended in a nuclear detonation. For this cohort, stage 2 triage will be very important but the type of biodosimetry depends on whether the irradiation occurred immediately or from fallout, because anyone from the detonation zones would more likely have physical injuries and/or burns and have received neutron exposures. Biodosimetry in stage 3 (medical care) would have only a modest role. Biodosimetry for people nearby but outside of the detonation and fallout zones requires a different approach, perhaps also benefitting from new methods.