International journal of radiation biology最新文献

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: This study aimed to optimize the preparation conditions and compare the UVB protection efficacy of three lipid-based nanocarrier formulations encapsulating enriched astaxanthin extract (ATXex) derived from Haematococcus pluvialis.

Materials and methods: The lipid-based nanocarriers encapsulating ATXex (Nano-ATXex) included nanoliposomes (NL), nanoemulsions (NE), and nanostructured lipid carriers (NLC). The formulations were prepared using a combination of ultrasonication and high-shear homogenization (for NE-ATXex), hot homogenization (for NLC-ATXex), or thin-film hydration (for NL-ATXex). Key parameters were evaluated to determine optimized preparation conditions, including surfactant ratios, lipid-to-surfactant ratios, and dispersion phase concentrations. The biological activities of the optimized Nano-ATXex formulations were evaluated using ABTS, MTT, γ-H2AX, and β-galactosidase assays, with in vivo UVB protection assessed in a murine model.

Results: All three Nano-ATXex formulations exhibited negative surface charge, spherical morphology, mean particle size of approximately 110 nm, PDI around 0.2, and high encapsulation efficiency exceeding 85%. The ABTS radical scavenging efficiency of Nano-ATXex was significantly higher than that of Trolox. Cytotoxicity was dependent on the lipid-based nanocarrier formulation and the concentration of ATXex. Biological activity evaluations demonstrated that NLC-ATXex significantly reduced the number of γ-H2AX foci per nucleus and the proportion of β-galactosidase-positive cells and mitigated UVB-induced skin damage more effectively than NE-ATXex and NL-ATXex.

Conclusions: Three successfully optimized Nano-ATXex formulations protected against UVB-induced DNA damage and senescence in vitro and alleviated skin damage in vivo, with NLC-ATXex showing the highest efficacy. The differences in cytocompatibility and biological activities indicated the importance of selecting an appropriate lipid-based nanocarrier formulation. These findings support the potential of ATXex-loaded nanocarriers in skin protection applications.

Background: In radiotherapy (RT), the dose given to the organs at risk (OAR) is as important as the dose received by the tumor. FF (Flattening Filtered) and FFF (Flattening Filter Free) treatment techniques used in RT offer different advantages in terms of their effects on target and critical organs. Treatment duration varies depending on the number of monitor units (MU) delivered per unit time. The aim of this study was to investigate biochemically and histopathologically the damage in healthy laryngeal tissue exposed to 600 MU/min FF and 2400 MU/min FF ionizing radiation under different fractionation protocols. Also to investigate the radioprotective effect of melatonin against the radiological damage.

Methods: The 78 rats included in the study were divided into 10 groups. Control and melatonin-only groups did not receive RT. The other 8 groups received FF and FFF ionizing radiation in different dose fractions. Half of the radiation group received melatonin 15 min before RT.

Results: No histological and biochemical differences were observed in the control and MLT only groups. Radiobiological damage was statistically significantly lower in the RT+MLT group compared to the RT only group.

Conclusions: It has been observed that melatonin has a protective effect against tissue damage caused by radiation exposure in healthy laryngeal tissue.

Purpose: Radiation-induced skin injury is a common complication that seriously affects the follow-up treatment and life quality of tumor patients. Nocardia rubra cell-wall skeleton (N-CWS) has been reported to have pro-angiogenesis effects, and its role on RISI remains unclear. The aim of this study was to investigate its effect on repair of radiation induced skin injury.

Materials and methods: After exposure to 45 Gy X-rays, the irradiated areas of SD rats were treated by N-CWS every 3 days. The radioprotective effects of N-CWS were evaluated by body weight changes, skin scores, H&E staining and TUNEL staining. Microvascular monitoring system and immunofluorescence staining of CD31 were performed to assess angiogenic capacity in vivo. In vitro, the activity and apoptosis of HUVECs were measured by CCK8 and flow cytometry. The angiogenic capacity of HUVECs was evaluated by tubule formation assay and Transwell assay. Western blot was performed to verify the possible mechanisms of the protective effect of N-CWS against radiation-induced skin damage.

Results: N-CWS was demonstrated to have low toxicity and radioprotective effects, maintained cell activity and attenuated radiation-induced apoptosis. In addition, N-CWS attenuated radiation-induced vascular injury in vivo and in vitro. Furthermore, P38 MAPK was shown to be associated with the radiation protection capability of N-CWS in HUVECs.

Conclusions: N-CWS promoted the repair of radiation-induced skin injury by enhancing angiogenesis, and the mechanism was related to the activation of P38 MAPK.

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: This study investigates the therapeutic potential of copper-doped carbon quantum dots (Cu-CQDs), integrating photothermal and photodynamic approaches to enhance cancer treatment efficacy.

Materials and methods: Cu-CQDs were synthesized using citric acid via a hydrothermal method. Nanoparticle characterization was conducted using dynamic light scattering (DLS), spectrofluorometry, and UV-Vis spectrophotometry. Photothermal performance was assessed by measuring temperature increases under laser irradiation. Photodynamic activity was evaluated by oxidative activity detection (consistent with reactive oxygen species (ROS) production) with 2,7-dichlorofluorescein diacetate. Cytotoxicity was examined against MCF-7 breast cancer cells, with and without the addition of 5-aminolevulinic acid (5-ALA) as a photosensitizer.

Results: The Cu-CQDs demonstrated a fluorescence quantum yield of 2.96%. Upon laser irradiation at 25 mg/mL, the temperature rose above 60 °C within 10 minutes, indicating effective photothermal performance. The cytotoxicity of the synthesized nanotherapeutic against MCF-7 cancer cells was evaluated, revealing that the combined photothermal and photodynamic effects (CQD + 5-ALA+LASER) resulted in 65% cell viability, which was significantly different from the cell viability obtained with the photothermal effect alone (CQD+LASER).

Conclusions: The study presents a promising cancer treatment strategy by combining photothermal and photodynamic effects of Cu-CQDs. This dual-function approach may serve as an effective method for future cancer therapies.

Purpose: To assess the protective effects of intragastric Vitamin C and N-acetylcysteine (NAC) against DNA damage from CT scan radiation in rats.

Materials and methods: The male Sprague Dawley rats (n = 8 per group) were allocated into four distinct groups: control (no CT radiation), IR (CT radiation only), Vitamin C (200 mg/kg with CT radiation), and NAC (200 mg/kg with CT radiation). Antioxidants were administered intragastrically 3 hours before scanning. Non-control groups underwent CT radiation at 120 kVp and 110 mA for 3 scans. Surface absorbed dose was measured with thermoluminescent dosimeter chips. Serum total antioxidant capacity (TAC) was measured pre- and post-scanning. γ-H2AX foci in peripheral blood lymphocytes were assessed at baseline, 1 hour, and 24 hours post-scan. Bone marrow smears were prepared 24 hours post-scan, stained with Giemsa, and micronucleus (MN) frequency in polychromatic erythrocytes was evaluated.

Results: TAC levels increased by 68.2% in the Vitamin C group and 152.3% in the NAC group compared to the IR group. γ-H2AX foci rates decreased by 10.3% in the Vitamin C group and 14.3% in the NAC group compared to the IR group. MN frequency decreased by 28.6% in the Vitamin C group and 34.9% in the NAC group compared to the IR group. No significant difference was found between Vitamin C and NAC.

Conclusion: Oral Vitamin C and NAC significantly mitigate radiation exposure from CT imaging in rats. Both antioxidants effectively reduce γ-H2AX foci and micronucleus formation, offering substantial protection against radiation-induced DNA damage.

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.

Background: Ionizing radiation (IR) disrupts redox balance and causes tissue injury through reactive oxygen species. Although the Nrf2-ARE pathway governs antioxidant defense, effective radioprotective activators remain limited. Hinokitiol, a natural antioxidant and anti-inflammatory tropolone, has not been previously evaluated in vivo for Nrf2-mediated radioprotection.

Methods: Forty male albino rats were divided into four groups: control, irradiated (8 Gy, fractionated), hinokitiol-only, and hinokitiol-pretreated + irradiated (Hinokitiol (10 mg/kg/day), by oral gavage). All parameters were assessed 24 hours after the final irradiation session.

Results: IR caused marked hematological suppression (reductions in RBCs, WBCs, platelets), hepatocellular injury (elevated ALT, reduced total protein), oxidative stress (increased MDA, NO, MPO), apoptosis, and downregulation of Nrf2-dependent genes. Hinokitiol pretreatment partially restored hematological parameters (platelets improved by over 20%, p = 0.026), reduced ALT by more than half, lowered NO and MPO levels, restored GSH, SOD, and CAT activities by more than 60% (p < 0.001), and decreased DNA fragmentation by nearly 50% (p < 0.01). Gene expression analysis revealed significant (p < 0.01) upregulation of Ho-1 , Nqo1, and Txnrd1 and significant (p < 0.01) suppression of Nf-κB and Tnf-α, consistent with Nrf2-ARE pathway activation and attenuation of inflammatory signaling. Histological analysis confirmed preserved hepatic architecture, supporting the liver's sensitivity to systemic oxidative injury and highlighting Hinokitiol's hepatic accumulation and protective effects.

Conclusion: These findings suggest, for the first time, that hinokitiol may activate the Nrf2-ARE pathway to counteract IR-induced oxidative stress, inflammation, and apoptosis, resulting in systemic protection. Hinokitiol emerges as a promising radioprotective candidate, warranting further investigation into its pharmacokinetics, toxicity profile, and translational potential as an adjunct in radiotherapy and other radiation exposure scenarios.

Introduction: Cancer risks of radiation are commonly made to evaluate an increase in mortality or incidence of cancers above background levels in subjects of the same age. However, the increased risk can also be evaluated by assuming a dose-dependent earlier onset expressed by a parallel shift of the mortality or incidence rate toward younger ages, which eventually results in life shortening.

Methods: Organ-specific relative risks for cancer was estimated by assuming that exposure to radiation increases the risk due to tissue reactions which subsequently facilitate an earlier onset of naturally occurring cancers. In this case, the years of earlier onset X can be obtained by examining the equation showing that the mortality or incidence rate for all cancers at age 70 in the 1 Gy-exposed group equals the rate at age 70 + X in the control group. In the present study, assuming that the X can be applied to all organs, organ-specific relative risk (RR)/Gy values were calculated as the ratio of the mortality or incidence rate at age 70 + X vs. at age 70 in the control group.

Results and discussion: The RR/Gy values thus obtained agreed closely with the epidemiologically estimated RR/Gy in major organs (stomach, colon, lung, liver etc.) while no clear evidence for an increased risk has been observed in the Life Span Study of atomic bomb survivors for pancreas, gallbladder, and kidney although the age-related patterns for the incidence or mortality of the control subjects are similar to those for the major organs. Possible reasons for the discrepancy are discussed.