International journal of radiation biology最新文献

Purpose: Cytogenetic biodosimetry of the Partial Body Irradiation (PBI) requires a dose response curve (DRC) for chromosome aberrations (ChA) but also an exponential coefficient D₀ of the interphase cell survival (ICS) of irradiated lymphocytes. The aim of the present work was to construct joint DRCs in vitro for ChA and ICS and validate them in a setting with a limited number of blood donors.

Materials & methods: Blood samples from three healthy volunteers were irradiated in vitro with 6 MV Linac photons to a range of acute doses up to 5.46 Gy. Cytogenetic preparations were stained with Fluorescence-plus-Giemsa; ChA were scored in the first division metaphases. The ICS was assessed in PBI simulations, mixing irradiated and unirradiated blood 1:1 at each dose point; D₀ was estimated by regression analysis.

Results: The DRC for dicentrics had linear and quadratic coefficients, respectively, 0.031 × cell^-1 × Gy^-1 and 0.070 × cell^-1 × Gy^-2; for dicentrics plus centric rings - respectively, 0.033 × cell^-1 × Gy^-1 and 0.083 × cell^-1 × Gy^-2. The ICS parameter D₀ varied within 3.18 - 3.54 Gy, depending on the end-point used for the assessment. DRCs were successfully validated in a biodosimetry exercise with uniform irradiation and PBI simulations in vitro and using in vivo data from four breast cancer patients after their first radiotherapy dose fraction.

Conclusions: Generating joint DRCs for ChA and ICS in a single experiment can be recommended as a rational methodology for laboratories practicing cytogenetic biodosimetry.

Purpose: Dr. Richard Hill performed pioneering work in the field of radiation-induced normal tissue injury to the lung including noninvasive imaging studies aimed at identifying imaging biomarkers of radiation-induced lung injury (RILI). RILI is a life-threatening toxicity of radiation exposure relevant to both cancer patients undergoing thoracic radiation therapy (RT) and victims of accidental radiation exposure. The ability to detect RILI noninvasively has the potential to guide treatment planning for RT and, in the case of victims of acute radiation exposures, inform the decision to start mitigative therapies. As part of this special issue of IJRB honoring Dr. Hill's many contributions to the field of radiation biology, this article reviews current advances in noninvasive imaging of RILI including computed tomography (CT), magnetic resonance (MR), hyperpolarized MR, nuclear medicine (PET and SPECT), and optical imaging with near-infrared (NIR) probes. Conclusion: The imaging modalities reviewed have potential to not only provide early identification of RILI but may also provide mechanistic insights into the progression of RILI via noninvasive detection of characteristic RILI mechanisms including: inflammation, vascular damage, cell death, oxidative stress, and fibrosis.

Purpose: Optimization of automated dicentric evaluation in the BIR laboratory is necessary to improve and accelerate individual biological dosimetry in radiation accident scenarios. Therefore, two different DCScore classifiers were analyzed for their suitability for use with laboratory-specific protocols, including two different lymphocyte culture conditions, 3-hour or 24-hour colcemid treatment.

Materials and methods: Dicentric formation was compared in 3 h and 24 h colcemid-treated cultures by fully- and semi-automated dicentric scoring using two different classifiers. Various calibration curves were constructed and absorbed doses of blinded X-irradiated blood samples were estimated after 24 h of colcemid treatment using both classifiers and scoring modes.

Results: 24 h colcemid treatment results in twice as many metaphases as 3 h colcemid treatment and the courses of dicentric frequencies after short- and long-term colcemid treatment differ, especially > 1 Gy. The "short-term colcemid classifier" detects more dicentric candidates and true positive dicentrics, respectively, especially > 2 Gy than the "long-term classifier" on the same slides.

Conclusion: Neither classifier was significantly better suited for the lab-specific MP preparations with regard to triage dose estimates for blinded samples by fully- as well as semi-automated analysis. For accurate dose assessment, it is recommended to adapt an available classifier to laboratory-specific conditions and protocols to optimize the identification of true dicentrics by DCScore.

Purpose: The aim of this study is to investigate the stability of radiation-induced electron paramagnetic resonance (EPR) signals in sorbitol and to determine the spectroscopic characteristics of the radiation-induced radicals in sorbitol.

Materials and methods: Sorbitol samples were irradiated at 10 Gy using a 6 MV X-ray beam of medical linear accelerator (LINAC). EPR measurements were carried out using X-band (Bruker ESR5000X, and EMX-131) and Q-band (Bruker EMXplus) spectrometers. Isochronal and isothermal annealing experiments, as well as fading experiments, were carried out to assess the stability of radiation-induced signals. EasySpin simulation software was used to determine the spectroscopic and structural parameters of the radiation-induced radicals.

Results: The EPR spectrum of irradiated sorbitol consists of several overlapping components produced by stable and unstable radicals. X- and Q-band measurements revealed significant changes in the signal patterns during time fading and thermal annealing experiments. High-temperature annealing caused rapid decay of the unstable radicals, leaving behind a stable radical. Simulation calculations indicated that at least three components were required to reproduce the observed EPR spectra. Spectroscopic parameters derived from simulations showed consistent agreement across the different experimental conditions.

Conclusion: Sorbitol shows promising characteristics as an EPR dosimeter, with radiation-induced radicals exhibiting distinct thermal and time stability. High-temperature annealing can eliminate unstable radicals, enabling reliable dosimetric application shortly after irradiation. The identified stable radical is a promising marker for dose quantification. These findings support the feasibility of using sorbitol for retrospective and accidental dosimetry.

Purpose: Our prior results showed that in the most cases, radiation doses measured by electron paramagnetic resonance (EPR) in tooth enamel samples significantly exceeded worksite reported doses. In an effort to understand causes of this discrepancy, we carried out EPR dose measurements in additional tooth samples collected from individuals studied before.

Materials and methods: Tooth enamel samples from five tissue donors to the United States Transuranium and Uranium Registries were used in this study. EPR measurements were performed using ELEXYS 500 spectrometer and high purity germanium detectors were used to measure gamma-emitting radionuclides.

Results: Significant variation of the EPR measured doses among multiple teeth collected from the same individuals was observed. These variations are potentially due to an additional exposure of the head/neck region as compared to the other parts of the body, e.g. torso where personal dosimeters are typically worn. The latter could explain very significant discrepancy of the doses, derived from EPR measurements and reported by worksites. With gamma-spectroscopy, no ¹³⁷Cs was detected in tooth roots.

Conclusions: In several cases there was nonuniform exposure of the head of the teeth' donors which may explain the discrepancy between worksite reported and EPR reconstructed doses. Results of the gamma counting suggested that exposure from ¹³⁷Cs in the roots was not a factor in the observed discrepancy.

Purposes: Hadrontherapy with proton and carbon ion scanning beams is an advanced radiation treatment modality mainly exploiting the finite range of those particles in the matter, to better spare critical organs close to the tumor volume as compared to photons. However, its complexity requires careful management of dosimetric uncertainties to guarantee patient safety. This study aims to reassess the suitability of alanine-based dosimetry for modern hadrontherapy applications.

Materials and methods: Alanine pellets based on electron spin resonance (ESR) were used as dosimeters. The response was taken from the peak-to-peak amplitude and compared to the ionization chamber one. Dose response and dependence on energy, beam direction, and linear energy transfer (LET), for both pristine Bragg peak and spread-out Bragg peak (SOBP) were evaluated. The ESR ratio x/y was evaluated as a function of LET and microwave power. Photon irradiations were performed with a 6 MV linear accelerator at the San Matteo Hospital, while with charged particles at CNAO, both located in Pavia, Italy.

Results: Alanine showed a linear dose-response for both protons and carbon ions in the range of 10-45 Gy. For carbon ions, a pronounced quenching effect in the Bragg peak and energy dependence were observed. Alanine effectiveness was reduced by up to 30% due to LET effects. Moreover, the use of the x/y ratio showed potential for LET differentiation.

Conclusions: Alanine may be a promising dosimeter for hadrontherapy. However, further studies are required to investigate factors of correction due to the effects of LET and energy dependence.

Purpose: Preserving the integrity of the genome is critical to healthy cellular growth and development. Under normal circumstances, the eukaryotic mismatch repair (MMR) machinery is effective at detecting DNA polymerase errors and maintaining the fidelity of the genome. However, cells with inactivated MMR machinery are prone to the accumulation of mutations and tumorigenesis. This study explores the theoretical potential of rhodium-99- and iodine-123-labeled DNA metalloinsertors as Auger electron-emitting radiotherapeutics for cancers characterized by MMR deficiency.

Materials and methods: A Monte Carlo code was developed in MATLAB^® to obtain Auger electron energy spectra for ⁹⁹Rh and ¹²³I. Using Geant4 track structure simulations, we determined the difference in effectiveness of these two Auger electron-emitting radionuclides in direct damage to DNA and the ability to produce double strand break damage (dsb) to the DNA comparing two different constructors 'G4EmDNAPhysics_option2' and 'G4EmDNAPhysics_option4'.

Results: Differences in the Auger electron emission spectra of ⁹⁹Rh and ¹²³I arise from their electronic structure: ¹²³I favors more complex cascades and ultra-low-energy electrons, while ⁹⁹Rh produces electrons with energies more suited to DNA damage. Despite similar total electron yields, the emissions of ⁹⁹Rh are more effective at causing dsb (0.71 vs. 0.60 dsb/decay for ⁹⁹Rh and ¹²³I, respectively, using constructor 'G4EmDNAPhysics_option2' and 0.81 dsb/decay for ⁹⁹Rh vs. 0.71 dsb/decay for ¹²³I when using 'G4EmDNAPhysics_option4'.

Conclusion: This theoretical study leverages both simulation and comparative analyses to identify ⁹⁹Rh as a promising Auger electron-emitting nuclide for radiotheranostics, as it offers superior DNA damage efficacy compared to ¹²³I.

Purpose: We developed a new computer program for the application of electron spin resonance (ESR) to dosimetry of wild animals related to the Fukushima Daiichi Nuclear Power Plant accident.

Materials & methods: The ESR spectra of carbonate radicals and other inorganic radicals are calculated by the complete elliptic integral. A simulated annealing method is implemented for the parameter optimization. A cost function is designed to include the second derivative form of the microwave absorption spectrum to improve the fitting accuracy. As a testing ground for the developed code, we prepared tooth enamel samples from a Japanese macaque captured in a control area.

Results: The developed code well reproduced the measured ESR spectrum. With a test spectrum, we demonstrated that the cost function that includes the second derivative form of the microwave absorption spectrum is helpful for the precise analysis of the low-dose enamel samples. The smoothness of the ESR spectrum plays an important role in utilizing this feature.

Conclusion: The developed computer code can be used to analyze the ESR spectrum of tooth enamels of Japanese macaques. A precise analysis is essential to lower the detection limit and expand the applicability of ESR dosimetry. The code is independent of the computer operating system and is available publicly.

Purpose: Cytogenetic biodosimetry is used for radiation dose assessment by evaluating chromosomal aberrations in peripheral blood lymphocytes. However, high-dose radiation may cause low absolute lymphocyte counts (ALCs), making it difficult to obtain sufficient metaphase spreads for analysis. This study aimed to optimize centrifugation settings to enrich metaphase spreads, particularly for lymphocytopenic patients.

Materials and methods: Peripheral blood samples from four healthy donors and one lymphocytopenic patient were collected. Lymphocytes were harvested using one of four centrifugation settings. After an additional low-speed centrifugation step (200 × g for 1 minute) in each experiment, we evaluated slide quality using mitotic index (MI) and metaphase frequency (MF), which were calculated by the number of metaphases and blasts using Metafer 4 software.

Results: We established an automatic measurement method for metaphases and blasts, adjusting the settings of Metafer 4. In four healthy donors, the strongest centrifugation (Exp. 4, 879 × g for 5 minutes) yielded the highest number of 'all cells' after harvest. Incorporating an additional low-speed centrifugation step significantly increased MF by 1.5- to 2-fold across all settings, with the greatest improvement observed in Exp. 4. This approach was applied to a lymphocytopenic patient, resulting in a 3.5-fold improvement of MF and the production of high-quality slides. MI was not significantly affected by centrifugation.

Conclusions: The combined high-speed and additional low-speed centrifugation method increased MF, improved slide quality by eliminating lower-density cells, and made it easier to analyze metaphase spreads. This method could be used for obtaining sufficient metaphase spreads in lymphocytopenic patients.

Purpose: To assess the radioecological consequences of the technogenic transformation of the Chornobyl NPP cooling pond aquatic ecosystem and its impact on the blood system of Myodes glareolus, a typical small rodent species in the Chornobyl exclusion zone.

Materials and methods: Animals were captured in the drained areas of the cooling pond and nearby areas. Radiometric surveys of the animals' natural habitat and soil sampling were conducted. γ-β-spectrometry was used to measure radionuclide levels (¹³⁷Cs and ⁹⁰Sr) in soil and animal bodies. Absorbed dose rates were calculated. Blood smears, bone marrow and spleen imprints were prepared and stained using the standard Pappenheim method.

Results: Activity of ¹³⁷Cs and ⁹⁰Sr in soil and animal samples, external/internal doses in animals were estimated. Radioecological assessment showed that radionuclide contamination in the drained areas did not exceed that of the adjacent territory. In exposed animals, similar hematopoietic alterations were observed, including disrupted differentiation and maturation of bone marrow cells, particularly in erythroid and granulocytic lineages. However, these blood abnormalities were less pronounced in animals from the drained zones.

Conclusions: Draining the cooling pond, despite the expected high radionuclide concentrations in bottom sediments, did not cause significant changes in surface soil contamination. While bank voles showed deviations in blood parameters compared to reference values, differences between exposure groups were generally not significant. These findings support continued monitoring of radiobiological effects associated with the transforming of radiation-contaminated aquatic ecosystems into terrestrial.