International journal of radiation biology最新文献

Introduction: Bacterial endospores are highly resistant to environmental stressors. Their resistance complicates sterilization efforts, leading to exploration of novel inactivation techniques. Radiation in the water window spectral range (284-543 eV), typically studied using synchrotron sources, offers high contrast for bio-imaging and potential for efficient spore inactivation due to its high absorption and shallow penetration.

Methods: A compact pulsed laser-plasma soft X-ray source was used to irradiate Bacillus subtilis spores in the water window spectral range. A combination of STEM-EDS and Geant4 Monte Carlo simulations provided data on spore geometry, elemental composition, and dose deposition. The spores were deposited on glass coverslips, dried, irradiated in vacuum, and resuspended for viability testing. Spore survival was assessed via colony-forming units, and the survival curve was fitted with a modified biphasic model.

Results: The decimation dose (D₁₀) was reached in less than one second at a 10 Hz repetition rate, indicating high inactivation efficiency. Effective photoabsorption coefficients were calculated from simulations and validated against tabulated values. Average dose rates in the spore core reached 2.4 kGy·s^-1, with peak values exceeding 10¹¹ Gy·s^-1. The survival curve exhibited biphasic kinetics with saturation behavior due to spore clustering.

Discussion: The study confirms that soft X-rays in the water window range are highly effective in rapidly inactivating bacterial spores. The efficiency is attributed to the spectral region's short attenuation lengths and high absorption cross-sections, aligning with data from conventional ionizing sources.

Purpose: The current work investigates the potential of exopolysaccharides (EPSs) and carotenoids produced from radioresistant bacteria as radioprotective agents.

Materials and methods: Twenty strains, isolated from gamma-irradiated roots of Cistanche violacea from Chott El-Djerid (Tunisia), were screened for EPSs and carotenoids production. The most EPS and carotenoids-producing bacterium was selected. The assessment of the impact of UVC-radiation dose effects on the synthesis of EPSs and carotenoids was investigated by response surface methodology (RSM). Both EPS and Carotenoids, from the strain CV6, were characterized by UV-Vis and Fourier transform infrared. The radioprotective potential of EPS and carotenoids on the survival of K. rosea CV6 following UVC dose was evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. Finally, in silico analyses of CV6's genome were assessed to identify the mechanisms involved in UVC protection.

Results: It was demonstrated that UVC irradiation of Kocuria rosea CV6 generated high amounts of EPSs and a carotenoid-producing strain. The assessment of the impact of radiation dose effects on the synthesis of EPSs and carotenoids by RSM shows that strain CV6 exhibited particular resistance to UVC radiation. The characterization of EPSs revealed the presence of six particular functional groups using Fourier transform infrared spectra. Pigments produced by CV6 were classified as carotenoids based on their spectroscopic characteristics. Also, the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide survival assay demonstrated a positive correlation between the concentrations of EPSs and carotenoids and viability of the UV-sensitive strain, Escherichia coli DH5α, following exposure to UVC radiation. In addition, the whole-genome analysis of the CV6 strain identified seven biosynthetic gene clusters encoding secondary metabolites, including those involved in the synthesis of EPSs and carotenoids.

Conclusion: The present investigation demonstrated that EPSs and carotenoids, extracted from K. rosea CV6, are promising bioactive components that could be used in the protection against UVC radiation.

Purpose: Carbonic anhydrase IX (CAIX), overexpressed in multiple cancers but limited in normal tissue, is a promising target for radionuclide therapy. This study evaluates [²¹²Pb]Pb-MKV-509, a novel DOTA-conjugated small-molecule ligand, for CAIX-targeted alpha therapy in preclinical renal carcinoma (SK-RC-52) and colorectal (HT-29) cancer models.

Materials and methods: [²¹²Pb]Pb-MKV-509 was assessed for radiochemical purity and stability. Binding assays determined receptor density and dissociation constants. Clonogenic survival, flow cytometry (viability, DNA damage, cell cycle), and spheroid assays (cross-sectional area, doubling time) evaluated biological responses. An in vivo biodistribution study was performed in SK-RC-52 xenograft-bearing mice, with and without carbonic anhydrase pre-blocking using acetazolamide.

Results: [²¹²Pb]Pb-MKV-509 exhibited high radiochemical purity (>96%) and stability for up to 48 h. Specific binding was higher in SK-RC-52 than in HT-29 cells. Treatment induced activity-dependent clonogenic inhibition, G2/M arrest, and DNA damage, with greater sensitivity observed in SK-RC-52 cells. Clonogenic survival was reduced by 50% at 3.4 kBq/mL (SK-RC-52) and 7.1 kBq/mL (HT-29). In spheroid models, 2.5-5.0 kBq/mL delayed growth and prolonged doubling time, indicating cross-fire effects. The biodistribution study revealed significant tumor uptake (4.7%IA/g at 2 h), along with high gastrointestinal accumulation. Pretreatment with acetazolamide partially reduced uptake in the stomach and intestines as well as in the tumor.

Conclusions: These findings highlight the potential of CAIX-targeted alpha therapy. CAIX expression and receptor density impact binding affinity and therapeutic response. The study demonstrates the importance of 3D tumor models in evaluating alpha-particle cross-fire effects. Further ligand optimization is warranted to enhance tumor specificity and minimize off-target uptake.

Purpose: Sprouting boosts bioactive compounds in Brassicaceae, including glucosinolates, amino acids, and anthocyanins. This study examined gamma radiation seed priming effects on growth, metabolism, and bioactive accumulation in Nasturtium officinale, Eruca sativa, and Raphanus raphanistrum sprouts.

Materials and methods: Seeds of the three species were primed with gamma radiation (0.1 kGy/h) and grown under controlled conditions. Biomass was measured; metabolic profiling quantified glucosinolates, amino acids, flavonoids, and anthocyanins. Enzymatic activities for glucosinolate and flavonoid biosynthesis were assessed. Antioxidant potential was assessed using FRAP and DPPH assays; antimicrobial activity was tested against Escherichia coli and Enterococcus faecalis. Microbial counts (APCs and Coliforms) were measured.

Results: Gamma radiation increased biomass by 48%, 36%, and 71% in N. officinale, E. sativa, and R. raphanistrum, respectively. Glucosinolates rose, especially glucoerucin (up to 227% in E. sativa) and glucoraphenin (up to 60%), linked to higher precursor amino acids (leucine, tryptophan, methionine), glutathione, and activities of glutathione S-transferase and sulfotransferase. Myrosinase activity increased, boosting sulforaphane. Flavonoids surged: quercetin (48 -191%), kaempferol (75 -172%), anthocyanins (42 -60%), with elevated PAL, CHS, 4CL, and C4H activities. Antioxidant and antimicrobial (40 -77%) potentials improved, though APCs and coliforms rose.

Conclusions: Gamma radiation priming enhances growth, secondary metabolite accumulation, antioxidant potential, and antimicrobial activity in Brassicaceae sprouts. It offers a promising method to improve the nutritional and functional qualities of edible sprouts, aiding food safety and health.

Aim: Glioblastoma (GBM) is an aggressive brain tumor characterized by resistance to temozolomide (TMZ) and radiotherapy. This study investigates the role of long non-coding RNA POT1-AS1 in modulating TMZ resistance (TMZR) and radiation-resistant (RR) in GBM by regulating ferroptosis via the IGF2BP2/glutathione peroxidase 4 (GPX4) pathway.

Methods: Human GBM cell lines, including TMZR and RR variants, were analyzed. POT1-AS1 expression was silenced using shRNA in U-87MG RR and U-87MG TMZR cells. The impact of POT1-AS1 knockdown on ferroptosis was evaluated by measuring iron concentration, reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) levels. GPX4 protein expression was also analyzed. Ferroptosis inhibition experiments were conducted using Fer-1. The stability of GPX4 mRNA was assessed by RNA immunoprecipitation (RIP) assays.

Results: POT1-AS1 and GPX4 were significantly overexpressed in U-87MG RR and TMZR cells. Knockdown of POT1-AS1 increased ferroptosis markers, including elevated iron and ROS levels, reduced GSH content, and downregulated GPX4 expression. POT1-AS1 knockdown sensitized GBM cells to TMZ and radiation. Additionally, the ferroptosis inhibitor Fer-1 reversed the effects of POT1-AS1 knockdown. RIP assays confirmed the interaction between POT1-AS1, IGF2BP2, and GPX4 mRNA, highlighting the POT1-AS1/IGF2BP2/GPX4 axis as a key regulator of ferroptosis.

Conclusions: POT1-AS1 promotes TMZ and radiation resistance in GBM by regulating ferroptosis through the IGF2BP2/GPX4 axis. Targeting this pathway may offer a new therapeutic strategy for overcoming GBM treatment resistance.

Purpose: This study aims to evaluate metabolic alterations in blood and urine samples from breast cancer patients undergoing adjuvant radiotherapy (RT) to identify potential biomarkers for radiation exposure and contribute to the development of biodosimetry tools, such as for use in nuclear incidents.

Materials and methods: Postmenopausal breast cancer patients (n = 20) undergoing postoperative RT were included in this prospective observational study. Blood and urine samples were collected at a total of six time points before, during, and after RT. Metabolic analysis was performed using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry and multivariable analyses, including partial least squares-discriminant analysis (PLS-DA) and random forest methodology, were used to identify discriminating metabolites. All analyses were performed using R version 4.1.2.

Results: Univariate analysis of blood samples showed significant downregulation of five metabolites during RT (week 5 + 6) compared to pre-RT: Hypoxanthine, 3-hydroxyisobutyric acid, L-lactic acid, pyruvic acid and xanthine (all p < .05). No statistically significant changes were found in urine samples. Multivariate analysis using PLS-DA identified a bundle of metabolites associated with radiation exposure, including diverse amino acids, purines, and bile acids. Extreme gradient boosting demonstrated moderate model performance in discriminating irradiated subjects with an AUC of 0.669 in blood samples.

Conclusions: This study identified several metabolites altered by RT in blood, providing insight into the metabolic impact of radiation exposure. These findings could provide a basis for developing diagnostic tools to detect radiation exposure. Further studies with larger and more diverse cohorts are needed to validate these biomarkers.

Purpose: The increasing use of Coronary CT Angiography (CCTA) raises concerns regarding radiation exposure and its associated cancer risks. This study aims to evaluate the effectiveness of the Siemens CARE kV algorithm in reducing radiation doses and cancer incidence risk compared to the Automatic Exposure Control (AEC) algorithm in adult patients undergoing CCTA.

Materials and methods: This retrospective study involved a cohort of 101 patients, comprising 55 women and 46 men, who underwent Siemens single-source 1 × 64-slice Multi-Detector CT (Somatom Definition AS) for CCTA. Demographic data and radiation dose parameters, including Computed Tomography Dose Index (CTDI_vol) and Dose-Length Product (DLP) were recorded. Effective and organ doses were calculated using ImPACT software, and Lifetime Attributable Risk (LAR) was estimated based on BEIR VII data.

Results: The Effective Doses (EDs) for AEC and CARE kV algorithms were 9.59 ± 3.84 mSv and 8.04 ± 3.99 mSv, respectively. The cancer incidence risk was significantly lower for the CARE kV algorithm, with LAR estimates of 7.27 ± 4.01 per 100,000 populations compared to 13.88 ± 10.76 for AEC. The CARE kV algorithm demonstrated a 27.07% reduction in LAR.

Conclusions: The findings suggest that the CARE kV algorithm provides a significant reduction in radiation exposure and associated cancer risks compared to the AEC algorithm. These results support the optimization of CT protocols to enhance patient safety while maintaining diagnostic efficacy.

Purpose: To assess the risk of thyroid nodules associated with prenatal radiation exposure.

Materials and methods: Thyroid screening was conducted among 1,439 Belarusians who were prenatally exposed to radioactive fallout from the Chernobyl nuclear plant accident. Estimated thyroid doses (mean, 0.14; median, 0.02 gray [Gy]) were predominately from intake of ¹³¹I. Binary logistic regression models were used to estimate excess odds ratios (EORs) for thyroid nodules associated with radiation dose.

Results: A total of 258 screening participants had one or more nonneoplastic thyroid nodules. Among all participants, there was a linear dose response with an EOR/Gy of 0.44 (95% CI: -0.01, 1.38) of borderline significance (p = .06). This was driven by a significant EOR/Gy of 0.84 (95% CI: 0.07, 2.45; p = .02) among participants who were in the third trimester at the time of the accident (ATA). No significant associations with radiation were found among those who were in the second or first trimester ATA, but there were considerable uncertainties. No significant differences in dose response were found by nodule size or multiplicity.

Conclusions: The significant risk of thyroid nodules associated with exposure in the third trimester indicates the presence of a vulnerable subgroup of pregnant women at the time of an accidental radioiodine release. Because of the strong correlation between gestational age and ¹³¹I dose in the fetal thyroid, the extent to which this excess risk is attributable to elevated ¹³¹I dose and/or radiosensitivity of the thyroid in later stage of fetal development remains unclear.

Purpose: Radon is a known human carcinogen and the second leading cause of lung cancer worldwide. This study evaluated the effectiveness of Radon Resistant New Construction (RRNC) ordinances enacted in Manheim Township, Pennsylvania, which mandate RRNC features in all new dwellings, to reduce lung cancer risk associated with radon exposure.

Materials and methods: We identified new dwellings in Manheim Township built under RRNC ordinances and analyzed corresponding radon test and mitigation data from PA DEP databases. After carefully reviewing the data and correcting database reporting anomalies, we evaluated indoor radon levels with and without RRNC and estimated the average reduction. Finally, we employed an existing dose-response model to estimate the average reduction of lung cancer risk associated with RRNC, taking smoking status into consideration.

Results: We analyzed 1,734 radon tests conducted in 483 homes, and found on average those homes built with RRNC features reduced the indoor radon concentration by 16.71 pCi/L and lowered the excess relative lung cancer risk attributable to radon exposure by 99%, regardless of smoking status.

Conclusions: Using real world data collected both before and after a change in municipal laws, these results provide strong evidence supporting the adoption of similar mandatory RRNC in other PA jurisdictions, nationwide, and in other countries that seek to reduce radon exposure and associated risks in indoor environment. This study demonstrates that the adoption and implementation of RRNC can reduce indoor radon levels, and consequently lower radon-related lung cancer risks.

Purpose: To confirm that the selection of a reference radiation affects the magnitude and range of the relative biological effectiveness (RBE) evaluations of neutron test radiation. Particular attention was paid to the published thermal neutron RBE dataset that is highly variable, with values ranging from 5.4-51.1.

Materials and methods: This involved a dual approach of 1) reaffirming dicentric chromosome assay (DCA) dose-response curve differences for ⁶⁰Co, ¹³⁷Cs, and 250 kVp X-rays, and 2) recalculating maximum RBE at minimal doses (RBE_M) for our previously reported neutron data, accompanied by an evaluation of reported studies that utilized two or more reference radiations.

Results and conclusions: The linear slope coefficient of the linear-quadratic dose-response curve, used to evaluate RBE_M, was found to be significantly different for ⁶⁰Co (0.0268 ± 0.0075 Gy^-1) compared to ¹³⁷Cs (0.0730 ± 0.0135, P < 0.01) and 250 kVp X-ray (0.1063 ± 0.0248, P < 0.01). Applying this finding to our previous thermal and fast neutron DCA evaluations, the RBE_M varied by a factor of 2.7 for ⁶⁰Co versus ¹³⁷Cs, and by a factor of four for ⁶⁰Co versus 250 kVp X-ray. A review of prior reported neutron RBE_M literature affirmed the finding that reference radiation selection can influence RBE_M magnitude. The selection of the reference radiation has implications for RBE evaluations of neutrons and other radiation qualities, as these RBE values underpin the radiation weighting factor, w_R, which informs radiation protection measures both terrestrially and in space. These experiments and reanalysis reconfirm and strongly demonstrate that reference radiation selection is a significant determinant of RBE variability, especially as applied to neutrons.