International journal of radiation biology最新文献

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: 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: Radiotherapy (RT) is a key treatment for localized prostate cancer (PCa); however, resistance and recurrence remain major challenges. Hyaluronan (HA), a key component of the extracellular matrix, has been implicated in cancer progression and therapeutic resistance. However, its role in the modulation of radiosensitivity, particularly in the tumor microenvironment, remains unclear. In this study, we aimed to investigate the role of HA in the radiosensitivity of PCa cells.

Materials and methods: 22Rv1 PCa epithelial cells and WPMY-1 myofibroblast cells were cultured to mimic tumor-stroma interactions. The effect on radiosensitivity was evaluated using colony formation assays. HA levels and molecular weight from cell culture supernatants were analyzed using enzyme-linked immunosorbent assays and agarose gel electrophoresis. Hyaluronidase expression was assessed using quantitative RT-PCR.

Results: WPMY-1 cells exposed to supernatants had significantly higher HA secretion than 22Rv1 cells. WPMY-1-derived HA enhanced the radioresistance of 22Rv1 cells, which was reversed by hyaluronidase. HA induced by 22Rv1-derived factors appears to be necessary for colony formation. The induced HA showed a shift toward a higher molecular weight owing to the downregulation of the degrading enzymes Hyal1 and PH20. The molecular weight of HA played a key role in modulating these effects.

Conclusion: Our findings suggest that stromal cells may contribute to the radioresistant tumor microenvironment in PCa partly through alterations in high-molecular-weight HA. While targeting HA metabolism holds potential to improve the efficacy of RT by disrupting this protective niche, further studies are needed to clarify the underlying mechanisms and validate these effects in vivo.

Purpose: This study aimed to investigate oxidative stress and histopathological changes in healthy rats after oral administration of I-131, to elucidate the mechanisms of gastrointestinal mucosal injury associated with radioiodine exposure, and provide translational insights relevant to clinical radioiodine therapy.

Materials and methods: Twenty-seven rats received I-131 (9.62 × 10⁶ Bq/100 µL) orally. Observations were made up to 7 days post-administration. Oxidative stress levels in the thyroid, small intestine, and stomach were measured using an enzyme-linked immunosorbent assay, while histopathological changes were analyzed using hematoxylin-eosin staining. Data were analyzed using one-way analysis of variance (SPSS v25).

Results and conclusion: Biochemical assays showed mild and inconsistent variations in antioxidant enzyme activity. H₂O₂ levels remained stable, whereas thyroid SOD activity exhibited a transient ∼22-fold increase within the first hour before returning to baseline by day 7, with no corresponding elevation in CAT or GPx. Histopathological evaluation revealed marked mucosal injury in the small intestine, characterized by epithelial erosion, edema, and inflammatory infiltration within 30 min, peaking at 2-3 h, and partially reappearing on days 5-7. In contrast, gastric lesions were milder and resolved completely by day 7. The discrepancy between biochemical stability and pronounced tissue injury suggests that localized oxidative stress may occur despite unchanged bulk reactive oxygen species levels, likely due to rapid compensatory antioxidant responses in healthy tissues. Overall, these findings underscore the importance of integrating biochemical and histological endpoints for a comprehensive assessment of radiation-induced toxicity. This integrated approach also supports further investigation into lipid peroxidation, protein oxidation, glutathione redox status, and mitochondrial function to elucidate the mechanisms underlying radioiodine-induced oxidative stress.

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.

Purpose: Low-dose-rate (LDR) radiation is known to induce subtle biological effects, but its impact on body fluid-based biomarkers remains poorly defined. This study evaluated dose rate-dependent hematological, biochemical, and immunological changes in blood, peritoneal lavage fluid (PLF), and bronchoalveolar lavage fluid (BALF) in healthy mice.

Materials and methods: Mice were exposed to whole-body LDR radiation at 0.39, 1.29, or 3.46 mGy/h for 21 days. Hematological analysis was performed on blood, and PLF and BALF were analyzed for biochemical and immune cell parameters.

Results: Most hematological indices were stable, except in the 3.46 mGy/h group, which showed significant changes in reticulocytes, white blood cells, lymphocytes, and platelet-large cell ratio. In PLF, alkaline phosphatase isoenzyme fraction (ALPIF) increased at 0.39 mGy/h, while AST, CK, and lactate were elevated at 1.29 mGy/h but normalized at 3.46 mGy/h. Immune analysis revealed increased polymorphonuclear cells and reduced lymphocytes in PLF at 0.39 mGy/h, indicating localized immune activation. In contrast, BALF showed no significant biochemical or cellular changes. A cross-compartment comparison of ALT, AST, and CK revealed hepatic or muscular stress in blood at 0.39 mGy/h, and localized metabolic alterations in PLF at 1.29 mGy/h.

Conclusions: LDR radiation induces non-linear, dose rate-specific effects on immune and metabolic parameters in blood and PLF, while BALF responses remain minimal. These findings highlight the utility of fluid-based biomarkers for early, minimally invasive detection of radiation-induced changes.

Background: When the same energy is delivered to a cellular target, DNA damage and the resulting cellular response may vary depending on the density and distribution pattern of the energy delivered to the critical volume of each cell. DNA damage can be quantitated based on the pattern of dose distribution over the sub-micrometer volumes in nucleus. DNA double-strand breaks (DSBs) are considered the most critical events for cellular effects. Local effect model (LEM), DNA damage model (DDM), and Giant LOop Binary LEsion (GLOBLE) model have been used to predict cell survival under radiation exposure.

Purpose: This study aims to implement computational modeling for prediction of cell survival under radiation exposure, by quantitating radiation events on cellular targets, such as local energy deposition and DSB production, in a unified frame. The conceptual bases of LEM, DDM, and GLOBLE model were adopted to derive parameters for radiation events.

Methods: The physics models of Geant4-DNA were used to simulate the interactions of X-rays and alpha particles with bio-matter. Cell nucleus was modeled to be a collection of ${(540\hspace{0.17em}\text{nm})}^3$ sub-volumes. Statistical variation of energy deposition to individual sub-volumes was analyzed to count DSB production and DSB multiplicity. Cell surviving fractions (SFs) were calculated by LEM based on the distribution of local doses to sub-volumes and by DDM and GLOBLE model based on the DSB production and their potential interactions in sub-volumes. Model parameters were derived by fitting the models to experimental data for rat diencephalon (RD) cells and rat gliosarcoma (RG) cells.

Results and conclusions: The overkill effect was reflected in the models based on LEM and DDM by employing threshold local dose and threshold number of DSBs in sub-volumes, respectively. Results suggest that the number of sub-volumes impacted with DSBs rather than the DSB multiplicity within individual sub-volumes would be better parameter to predict cell killing effect, which complies with the GLOBLE model.

Purpose: The fast diagnosis of the life-threatening acute radiation syndrome is crucial, as the early prediction of the hematological acute radiation syndrome (H-ARS) can save lives. Previously, we validated a four-gene set (FDXR, DDB2, POU2AF1, WNT3) for H-ARS severity prediction in non-human primates and leukemia patients. In this study, we aim to validate this gene set in minipigs as a surrogate model.

Materials and methods: 12 Göttingen minipigs, irradiated with 1.8 or 2.1 Gray (LD_≈40/30), were examined. METREPOL H-ARS severity degrees were determined using sequential blood cell count changes over time after irradiation. For quantitative Real-Time-PCR (qRT-PCR), peripheral whole blood was withdrawn before and on days 1, 3, and 10 after irradiation. Normalization was performed using 18S rRNA and PUM1 as housekeeping genes (HKG). Differential gene expression (DGE) relative to the pre-irradiated samples was calculated.

Results: All minipigs developed a 2-4 H-ARS-severity degree. 18S rRNA revealed significantly (p = .0005) about two-fold higher variance of raw Ct-values than PUM1. DGE was calculated for all genes except WNT3 (undetectable in most animals). All genes revealed a slight up-regulation over time in most animals, but DGE > 2 regarding FDXR or DDB2 and concomitant downregulation of POU2AF1 (DGE < 0.5) as expected given the H-ARS severity degrees, was not observed.

Conclusion: None of the animals revealed the expected DGE pattern corresponding to a moderate to high H-ARS-severity degree. Hence, the Göttingen minipig did not qualify as another validation model for our specific gene set, which does not argue against their validity for other purposes.

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.