Influence of 60Co gamma radiation on the structural, morphological and optical properties of hydrothermally synthesized MoO3-CeO2 nanocomposite.

The influence of 60Co gamma radiation on Molybdenum Oxide-Cerium Oxide (MoO3-CeO2) nanocomposite is investigated in the present study. The MoO3-CeO2 nanocomposite was synthesized by conventional hydrothermal route. Ammonium hepta molybdate tetrahydrate [(NH4)6Mo7O24.4H2O] and cerium nitrate [Ce (NO3)3.4H2O] were used as the precursors. The composite was subjected to high energy gamma irradiation for different doses of 50, 100 and 150 kGy using 60Co gamma irradiation chamber. The structural study was carried out using X-ray diffraction, the morphological studies were carried out using scanning electron microscopy and ultraviolet-visible spectroscopy was carried out to study the optical properties before and after irradiation. The crystallite size was found to increase with increasing doses of gamma irradiation. The morphology of the samples shows that the nanoparticles tend to agglomerate with increasing doses of gamma radiation. The energy bandgap of the MoO3-CeO2 nanocomposite was calculated before and after irradiation and found to decrease with increasing doses of irradiation upto 100 kGy and then increases for 150 kGy.

Complex Long-term Effects of Radiation on Adult Mouse Behavior.

We have shown previously that a single radiation event (0.063, 0.125 or 0.5 Gy, 0.063 Gy/min) in adult mice (age 10 weeks) can have delayed dose-dependent effects on locomotor behavior 18 months postirradiation. The highest dose (0.5 Gy) reduced, whereas the lowest dose (0.063 Gy) increased locomotor activity at older age independent of sex or genotype. In the current study we investigated whether higher doses administered at a higher dose rate (0.5, 1 or 2 Gy, 0.3 Gy/min) at the same age (10 weeks) cause stronger or earlier effects on a range of behaviors, including locomotion, anxiety, sensorimotor and cognitive behavior. There were clear dose-dependent effects on spontaneous locomotor and exploratory activity, anxiety-related behavior, body weight and affiliative social behavior independent of sex or genotype of wild-type and Ercc2S737P heterozygous mice on a mixed C57BL/6JG and C3HeB/FeJ background. In addition, smaller genotype- and dose-dependent radiation effects on working memory were evident in males, but not in females. The strongest dose-dependent radiation effects were present 4 months postirradiation, but only effects on affiliative social behaviors persisted until 12 months postirradiation. The observed radiation-induced behavioral changes were not related to alterations in the eye lens, as 4 months postirradiation anterior and posterior parts of the lens were still normal. Overall, we did not find any sensitizing effect of the mutation towards radiation effects in vivo.

Development of hematopoietic syndrome mice model for localized radiation exposure.

Current models to study the hematopoietic syndrome largely rely on the uniform whole-body exposures. However, in the radio-nuclear accidents or terrorist events, exposure can be non-uniform. The data available on the non-uniform exposures is limited. Thus, we have developed a mice model for studying the hematopoietic syndrome in the non-uniform or partial body exposure scenarios using the localized cobalt60 gamma radiation exposure. Femur region of Strain 'A' male mice was exposed to doses ranging from 7 to 20 Gy. The 30 day survival assay showed 19 Gy as LD100 and 17 Gy as LD50. We measured an array of cytokines and important stem cell markers such as IFN-γ, IL-3, IL-6, GM-CSF, TNF-α, G-CSF, IL-1α, IL-1ß, CD 34 and Sca 1. We found significant changes in IL-6, GM-CSF, TNF-α, G-CSF, and IL-1ß levels compared to untreated groups and amplified levels of CD 34 and Sca 1 positive population in the irradiated mice compared to the untreated controls. Overall, we have developed a mouse model of the hematopoietic acute radiation syndrome that might be useful for understanding of the non-uniform body exposure scenarios. This may also be helpful in the screening of drugs intended for individuals suffering from radiation induced hematopoietic syndrome.

Oxidative stress associated metabolic adaptations regulate radioresistance in human lung cancer cells.

Differential inherent and acquired radioresistance of human lung cancer cells contribute to poor therapeutic outcome and tumor recurrence after radiotherapy. Inherent radioresistance of lung cancer cells is known to be associated with ROSLow cancer stem cells (CSCs). However, mechanism of acquired radioresistance in lung cancer cells is poorly understood. Here, we exposed human lung cancer cells (A549) to a cumulative dose of 40Gy and allowed the radioresistant (RR) survivors to divide and form macroscopic colonies after each fraction of 5Gy dose. The RR subline exhibited enrichment of cytosolic ROSHigh cells without specific increase in mitochondrial ROS levels. We found a concomitant increase in the expression of redox regulatory transcription factor Nrf2 and its dependent antioxidant genes in RR cells and cell cycle delay as compared to parental cells. The treatment of RR cells with Nrf2 inhibitor resulted in decreased clonogenic survival indicating their addiction to Nrf2 for metabolic adaptations under high levels of cytosolic ROS. A causal role of inherent ROS levels in conferring radioresistance was established by sorting ROSHigh and ROSLow populations from parental and RR cells. It was observed that ROSHigh population from both parental and RR cells exhibited radioresistance as observed by clonogenic assay. Interestingly, ROSHigh population of cells exhibited higher levels of cellular thiols in both parental and RR cells. Thus, our observations highlight presence of a novel subpopulation in lung cancer cells, which exhibits radioresistance by maintaining 'oxidative stress' and Nrf2 dependent metabolic adaptations. We also posit Nrf2 pathway as a druggable target for radiosensitization of RR A549 cells.

Gamma radiation-induced preparation of chitosan-acrylic acid-1-vinyl-2-vinylpyrrolidone/multiwalled carbon nanotubes composite for removal of 152+154Eu, 60Co and 134Cs radionuclides.

Removal behaviors of 152+154Eu, 60Co, and 134Cs radionuclides onto Chitosan-acrylic acid-1-vinyl-2-vinylpyrrolidone/oxidized multi-walled carbon nanotubes (CTS-AA-VP/o-MWCNTs) composite has been investigated by batch adsorption technique. CTS-AA-VP/o-MWCNTs composite has been synthesized by copolymerization of acrylic acid (AA) and 1-vinyl-2-vinylpyrrolidone (VP) onto the surface of chitosan/oxidized multi-walled carbon nanotubes (CTS/o-MWCNTs) using gamma radiation. SEM, TGA, and FTIR were applied to characterize the morphology, thermal stability, and structure of the composite. The composite shows high removal capacity of 321.77, 369.91, and 456.46 mg/g towards 152+154Eu, 60Co, and 134Cs radionuclides, respectively.

Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules.

HER3-binding affibody molecules are a promising format for visualization of HER3 expression. Cobalt-55, a positron-emitting isotope, with a half-life of 17.5 h, allows for next-day imaging. We investigated the influence of the charge of the radiocobalt-chelator complex on the biodistribution of anti-HER3 affibody molecule (HE)3-ZHER3 and compared the best radiocobalt-labeled variant with a recently optimized gallium-labeled variant. Affibody conjugates (HE)3-ZHER3-X (X = NOTA, NODAGA, DOTA, DOTAGA) were labeled with [57Co]Co (surrogate for 55Co). Affinity measurements, binding specificity and cellular processing were studied in two HER3-expressing cancer cell lines. Biodistribution was studied 3 and 24 h post-injection (pi) in mice with HER3-expressing BxPC-3 xenografts and compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA. Micro-single-photon emission tomography/computed tomography (microSPECT/CT) and micro-positron emission tomography/computed tomography (microPET/CT) imaging was performed 3 and 24 h pi. Stably labeled conjugates bound to HER3 with subnanomolar affinity. [57Co]Co-(HE)3-ZHER3-DOTA had the best tumor retention and a significantly lower concentration in blood than other conjugates, leading to superior tumor-to-blood and tumor-to-liver ratios 24 h pi. Compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA 3 h pi, [57Co]Co-(HE)3-ZHER3-DOTA provided superior imaging contrast in liver 24 h pi. Concluding, the composition and charge of the [57Co]Co-chelator complex influenced the uptake in tumors and normal tissue. [57Co]Co-(HE)3-ZHER3-DOTA provided the best imaging properties among the cobalt-labeled conjugates. Delayed imaging of HER3 expression with [57Co]Co-(HE)3-ZHER3-DOTA improved imaging contrast compared to early-time-point imaging with [68Ga]Ga-(HE)3-ZHER3-NODAGA.

Reference dose determination in 60Co and high-energy radiotherapy photon beams by using Farmer-type cylindrical ionization chambers - an experimental investigation.

Ionization chamber dosimetry is predominantly used for determination of the absorbed dose to water in 60Co and high-energy radiotherapy photon beams. The most widespread ionization chambers employed for absolute or reference dose determinations in reference conditions are the Farmer-type cylindrical ionization chambers. The Farmer-type ionization chambers have a variety of constructions and materials and their responses vary in the radiation beam. Clinical accelerators, in addition to conventional photon beams with flattening-filter, can also deliver flattening-filter-free (FFF) photon beams. The responses of five different Farmer-type cylindrical ionization chambers were experimentally examined with reference to absorbed dose determination in reference conditions when using the International Atomic Energy Agency (IAEA) - American Association of Physicists in Medicine (AAPM) Technical Reports Series no. 483 (TRS-483) and the IAEA TRS-398 dosimetry protocol in the present investigation. The irradiations were performed using 60Co and megavoltage photon beams with 6 MV, 15 MV, 6 MV FFF and 10 MV FFF nominal photon energies. The chamber calibrations were performed at different Secondary Standard Dosimetry Laboratories and are traceable to primary standards at different Primary Standard Dosimetry Laboratories. The chambers were also cross-calibrated at our laboratory using 60Co γ-beam. The variation found in the data regarding the reference dose determination using the various Farmer-type chambers in the photon beams employed was about 1% at maximum. Thus, the selection of the ionization chamber in reference dose determinations may affect the outcomes. The differences in the absorbed dose values were similar in the conventional as well as in the FFF photon beams. For the FFF photon beams the absorbed dose computations were performed using the IAEA-AAPM TRS-483 dosimetry protocol. Two of the ionization chambers used had identical construction but different central electrodes, i.e. graphite versus aluminium. The results obtained using these two chambers show that, in the photon beams examined, the employed correction for the central electrode (p cel ) regarding these two chambers is associated with an inaccuracy which is larger than the calculated uncertainty for this correction. The outcomes found in the present experimental investigation using the various ionization chambers also indicate possible inaccuracy in the employed beam quality correction factors (k Q ) and imply the need for a revision of these factors.

In vivo dosimetry using MOSkin detector during Cobalt-60 high-dose-rate (HDR) brachytherapy of skin cancer.

The MOSkin, a metal-oxide semiconductor field-effect transistor based detector, is suitable for evaluating skin dose due to its water equivalent depth (WED) of 0.07 mm. This study evaluates doses received by target area and unavoidable normal skin during a the case of skin brachytherapy. The MOSkin was evaluated for its feasibility as detector of choice for in vivo dosimetry during skin brachytherapy. A high-dose rate Cobalt-60 brachytherapy source was administered to the tumour located at the medial aspect of the right arm, complicated with huge lymphedema thus limiting the arm motion. The source was positioned in the middle of patients' right arm with supine, hands down position. A 5 mm lead and 5 mm bolus were sandwiched between the medial aspect of the arm and lateral chest to reduce skin dose to the chest. Two calibrated MOSkin detectors were placed on the target and normal skin area for five treatment sessions for in vivo dose monitoring. The mean dose to the target area ranged between 19.9 and 21.1 Gy and was higher in comparison with the calculated dose due to contribution of backscattered dose from lead. The mean measured dose at normal skin chest area was 1.6 Gy (1.3-1.9 Gy), less than 2 Gy per fraction. Total dose in EQD2 received by chest skin was much lower than the recommended skin tolerance. The MOSkin detector presents a reliable real-time dose measurement. This study has confirmed the applicability of the MOSkin detector in monitoring skin dose during brachytherapy treatment due to its small sensitive volume and WED 0.07 mm.

Independent assessment of source transit time for the BEBIG SagiNova® cobalt-60 high dose rate brachytherapy afterloader.

Independent verification of transit time and the methodology employed in commercial high dose rate (HDR) afterloaders to compensate its effect is an important part of their commissioning and quality assurance. This study aimed to independently evaluate the Co-60 source transit time of the new BEBIG SagiNova® HDR afterloader unit by employing a dosimetric approach using a well-type ionization chamber. The source was placed at three dwell positions (DPs) to mimic a variety of clinical situations with different distances from the afterloader unit. The distances of the DPs to the afterloader were 129.37 cm, 124.50 cm and 118.57 cm. Plans were generated using the SagiPlan® treatment planning system to produce 3, 5, 10, 15, 20, 30, 40, 60 and 120 s dwell times (DTs). The residual transit times (following any possible system compensation) were assessed using the ESTRO-recommended approach of obtaining transit time compensation factors and another strategy established for teletherapy sources. The mean residual transit time depended on the distance between the afterloader and the DP, ranging from 0.43 to 1.10 s. The transit dose contribution was case-specific, ranging from 0.4% for a 60 s DT at the nearest DP to the afterloader up to 15.6% for a 3 s DT at the furthest DP from the unit. The results show that currently SagiNova® afterloader does not apply transit time compensation and suggest a 0.2-0.5 s compensation for each arrival and departure DP from/to the afterloader, depending on position in an 11 cm active length.

Dose-dependent 60Co γ-radiation Effects on Human Endothelial Cell Mechanical Properties.

Exposure to ionizing radiation is unavoidable for noncancerous cells during the external radiotherapy process. Increasing the dose delivery fraction times leads to increasing the endothelial cell damage. Vascular abnormalities are commonly associated with the alternation of endothelium biomechanical properties. The goal of the present study was to quantify the elastic and viscoelastic properties of human umbilical vein endothelial cells (HUVECs) using the micropipette aspiration technique in conjunction with a theoretical model while an 8 Gy dose was given in four fractions. Confocal imaging was performed for evaluation of cytoskeletal changes during fractionation 60Co radiotherapy. The results indicated an increase in elastic modulus from 29.87 ± 1.04 Pa to 46.69 ± 1.17 Pa while the fractional doses increased from 0 Gy to 8 Gy along with the obvious cytoskeletal changes. Moreover, in the creep behavior of radiated groups, a significant decrease was shown in the time constant and viscoelastic properties. On the other hand, it was observed that the change in the biomechanical properties of the cells while applying a single fraction of 8 Gy was not exactly the same as that in the properties of the radiation-exposed cells while delivering an 8 Gy dose at 2 Gy per fraction. The observed differences in the biomechanical behavior of endothelium provide a quantitative description of radiobiological effects for evaluating the dose-response relationship as a biological dosimetry procedure.

Monte Carlo modeling of a 60Co MRI-guided radiotherapy system on Geant4 and experimental verification of dose calculation under a magnetic field of 0.35 T.

Our purpose was to establish the commissioning procedure of Monte Carlo modeling on a magnetic resonance imaging-guided radiotherapy system (MRIdian, Viewray Inc.) under a magnetic field of 0.345 T through experimental measurements. To do this, we sought (i) to assess the depth-dose and lateral profiles generated by the Geant4 using either EBT3 film or the BJR-25 data; (ii) to assess the calculation accuracy under a magnetic field of 0.345 T. The radius of the electron trajectory caused by the electron return effect (ERE) in a vacuum was obtained both by the Geant4 and the theoretical methods. The surface dose on the phantom was calculated and compared with that obtained from the film measurements. The dose distribution in a phantom having two air gaps was calculated and measured with EBT 3 film. (i) The difference of depth-dose profile generated by the Geant4 from the BJR-25 data was 0.0 ± 0.8% and 0.3 ± 1.5% for field sizes of 4.5 and 27.3 cm2, respectively. Lateral dose profiles generated by Geant4 agreed well with those generated from the EBT3 film data. (ii) The radius of the electron trajectory generated by Geant4 agreed well with the theoretical values. A maximum of ~50% reduction of the surface dose under a magnetic field of 0.345 T was observed due to elimination of the electron contamination caused by the magnetic field, as determined by both the film measurements and the Geant4. Changes in the dose distributions in the air gaps caused by the ERE were observed on the Geant4 and in the film measurements. Gamma analysis (3%/3 mm) showed a pass rate of 95.1%. Commissioning procedures for the MRI-guided radiotherapy system on the Geant4 were established, and we concluded that the Geant4 had provided high calculation accuracy under a magnetic field of 0.345 T.

Evaluation of optically stimulated luminescence dosimeter for exit dose in vivo dosimetry in radiation therapy.

AIM: The aim of this study was to assess and analyze the exit dose in radiotherapy using optically stimulated luminescence dosimeter (OSLD) with therapeutic photon beams. MATERIALS AND METHODS: Measurements were carried out with OSLD to estimate the exit dose in phantom for different field sizes, various phantom thicknesses, and with added backscatter material. The data obtained were validated with ionization chamber data where applicable. A correction factor was found to determine the actual dose delivered at the exit surface using measured and theoretical dose. RESULTS: The exit dose factor with Co-60, 6 MV, and 18 MV beams for 10 cm phantom thickness was found to be 0.752 ± 0.38%, 0.808 ± 0.34%, and 0.882 ± 0.42%. The dose enhancement factor with field size was ranging from 3% to 7.7% for Co-60 beam, from 2.6% to 6.6% for 6 MV, and from 2.5% to 4.7% for 18 MV beams at 10 cm depth of the phantom with 20 cm backscatter. The percentage reduction in exit dose with no backscatter material at 25 cm depth with field size of 10 cm × 10 cm was 5.6%, 4.4%, and 4.0%, less than the dose with full backscatter thickness of 20 cm for Co-60 beam, 6 MV, and 18 MV beam. CONCLUSIONS: The promising results confirm that accurate in vivo exit dose measurements are possible with this potential dosimeter. This technique could be implemented as a part of quality assurance to achieve quality treatment in radiotherapy.

Dosimetric characterisation of the optically-stimulated luminescence dosimeter in cobalt-60 high dose rate brachytherapy system.

This study investigates the characteristics and application of the optically-stimulated luminescence dosimeter (OSLD) in cobalt-60 high dose rate (HDR) brachytherapy, and compares the results with the dosage produced by the treatment planning system (TPS). The OSLD characteristics comprised linearity, reproducibility, angular dependence, depth dependence, signal depletion, bleaching rate and cumulative dose measurement. A phantom verification exercise was also conducted using the Farmer ionisation chamber and in vivo diodes. The OSLD signal indicated a supralinear response (R2 = 0.9998). It exhibited a depth-independent trend after a steep dose gradient region. The signal depletion per readout was negligible (0.02%), with expected deviation for angular dependence due to off-axis sensitive volume, ranging from 1 to 16%. The residual signal of the OSLDs after 1 day bleached was within 1.5%. The accumulated and bleached OSLD signals had a standard deviation of ± 0.78 and ± 0.18 Gy, respectively. The TPS was found to underestimate the measured doses with deviations of 5% in OSLD, 17% in the Farmer ionisation chamber, and 7 and 8% for bladder and rectal diode probes. Discrepancies can be due to the positional uncertainty in the high-dose gradient. This demonstrates a slight displacement of the organ at risk near the steep dose gradient region will result in a large dose uncertainty. This justifies the importance of in vivo measurements in cobalt-60 HDR brachytherapy.

A PSMA Ligand Labeled with Cobalt-55 for PET Imaging of Prostate Cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) comprises a recognized target for molecular imaging of prostate cancer. As such, radiolabeled PSMA inhibitors are of great value for diagnosis and staging of this disease. Herein, we disclose the preclinical characterization of [55Co]PSMA-617 for positron emission tomography (PET)/x-ray computed tomography (CT) imaging of prostate cancer lesions. PROCEDURES: By the application of microwave heating, PSMA-617 in acetate buffer (0.4 M, pH 4.4) was labeled with the radioisotopes cobalt-55/57. The extents of internalization and dissociation constants (K D) were determined against 2-(phosphonomethyl)-pentanedioic acid in two PSMA-positive cell lines, LNCaP, and PC3-PIP, with [57Co]PSMA-617 as a surrogate for [55Co]PSMA-617 (T½ 17.5 h, ß max 1.5 MeV, Iß 76 %). The biodistribution in LNCaP xenograft mice was investigated using [57Co]PSMA-617 and [55Co]PSMA-617 was employed for PET/CT imaging at 1, 4, and 24 h and compared to PET/CT scans using [68Ga]PSMA-617. RESULTS: The radiolabeling with cobalt-55/57 was performed in yields greater than 99.5 and 99.8 % and radiochemical purities of 99.7 and 98.9 %, respectively. The molar-specific activities were 18.2 MBq/nmol and 3.3 MBq/nmol. The cellular K D were determined to be 4.7 nM for LNCaP and 9.8 nM for PC3-PIP, correspondingly. Internalization of 76 and 71 % of the cell-associated radioactivity was found for LNCaP and PC3-PIP cells after incubation up to 240 min, respectively. In regard to the biodistribution in LNCaP xenograft mice, [57Co]PSMA-617 displayed a high and relatively constant uptake in the tumor (12.9 %IA/g at 1 h to 10.5 %IA/g at 24 h) with an initial but transient high uptake in the kidneys, adrenals, and spleen. Tumor-to-background ratios improved over time as normal tissue cleared of the radioligand (tumor-to-blood: 26, 258, and 3013; tumor-to-kidney: 0.11, 0.28, and 4.3 at 1, 4, and 24 h). PET/CT imaging with [55Co]PSMA-617 in xenograft mice confirmed the high tumor uptake and fast clearance of normal tissues over time and was found superior to imaging with [68Ga]PSMA-617. CONCLUSION: Radiolabeling of PSMA-617 was achieved in excellent yields and radiochemical purities. Favorable in vitro data comprising low K D values and high extent of internalization was determined for two PSMA-positive cell lines. In xenograft mice, high tumor accumulation and excellent tumor-to-normal tissues ratios were established by biodistribution experiments and PET/CT imaging and, hence, confirm the potential of [55Co]PSMA-617 for delayed clinical imaging of prostate cancer.

Monte Carlo simulation of the RBE of I-131 radiation using DNA damage as biomarker.

In general, a weighting factor of one is applied for low linear energy transfer radiations. However, several studies indicate that relative biological effectiveness (RBE) of low energy photons and electrons is greater than one. The aim of this current study was calculating the RBE of I-131 radiation relative to Co-60 gamma photons in 100 µm spheroid cells using Monte Carlo (MC) simulations. These calculations were compared to experimentally measured results. MCNPX2.6 was used to simulate the I-131 and Co-60 irradiation setups and calculate the secondary electron spectra at energies higher than 1 keV with varying oxygen concentrations. The electron spectra at energies lower than 1 keV were obtained by extrapolation (down to 10 eV). The calculated electron spectra were input into the MCDS micro-dosimetric Monte Carlo code to calculate the DSB induction and related RBE. The calculated RBE of I-131 radiation relative to Co-60 photons, as the reference radiation recommended by the International Commission on Radiation Protection (ICRP), was 1.06, 1.03 and 1.02 for oxygen concentrations of 0, 5 and 100%, respectively. Results of MC simulations indicate the RBE of I-131 is greater than one. This finding, despite a 10% discrepancy with the findings of the previous in vitro study of one of the authors of this paper, reemphasizes that I-131 radiation induces more severe biological damage than current ICRP recommendations.

Succinate ester derivative of δ-tocopherol enhances the protective effects against 60Co γ-ray-induced hematopoietic injury through granulocyte colony-stimulating factor induction in mice.

α-tocopherol succinate (α-TOS), γ-tocotrienol (GT3) and δ-tocotrienol (DT3) have drawn large attention due to their efficacy as radioprotective agents. α-TOS has been shown to act superior to α-tocopherol (α-TOH) in mice by reducing lethality following total body irradiation (TBI). Because α-TOS has been shown to act superior to α-tocopherol (α-TOH) in mice by reducing lethality following total body irradiation (TBI), we hypothesized succinate may be contribute to the radioprotection of α-TOS. To study the contributions of succinate and to identify stronger radioprotective agents, we synthesized α-, γ- and δ-TOS. Then, we evaluated their radioprotective effects and researched further mechanism of δ-TOS on hematological recovery post-irradiation. Our results demonstrated that the chemical group of succinate enhanced the effects of α-, γ- and δ-TOS upon radioprotection and granulocyte colony-stimulating factor (G-CSF) induction, and found δ-TOS a higher radioprotective efficacy at a lower dosage. We further found that treatment with δ-TOS ameliorated radiation-induced pancytopenia, augmenting cellular recovery in bone marrow and the colony forming ability of bone marrow cells in sublethal irradiated mice, thus promoting hematopoietic stem and progenitor cell recovery following irradiation exposure. δ-TOS appears to be an attractive radiation countermeasure without known toxicity, but further exploratory efficacy studies are still required.

Up-Regulated ATF4 Expression Increases Cell Sensitivity to Apoptosis in Response to Radiation.

BACKGROUND/AIMS: Activating transcription factor 4 (ATF4) is a member of the activating transcription factor family which regulates the expression of genes involved in amino acid metabolism, redox homeostasis and ER stress responses. ATF4 is also over-expressed in human solid tumors, although its effect on responsiveness to radiation is largely unexplored. METHODS: Real-time PCR was used to detect ATF4 mRNA levels in cells treated with different doses of 60Coγ radiation. Cell viability was assayed using a cell counting kit. The cell cycle was analyzed using flow cytometry, and cell apoptosis was assayed using Annexin V-PI double labeling. Small interfering RNA (siRNA) against ATF4 was transfected into ECV304 cells using Lipofectamine 2000. An ATF4 over-expression plasmid (p-ATF4-CGN) was transfected into HEK293 cells that endogenously expressed low levels of ATF4. The levels of intracellular reactive oxygen species (ROS) were measured using CM-H2DCFDA as a probe. RESULTS: ATF4 mRNA and protein expression levels were higher after radiation and increased in a dose- and time-dependent manner in AHH1 lymphoblast cells (P < 0.05). An increase in ATF4 levels was also observed after radiation in primary murine spleen cells, human endothelial ECV304 cells, human liver LO2 cells, breast cancer MCF7 cells, and human hepatocellular carcinoma HEPG2 cells. No change was observed in human embryonic kidney 293 (HEK293) cells. Over-expressing ATF4 in HEK293 cells inhibited cell proliferation, increased cell apoptosis and significantly increased the proportion of cells in G1 phase. Conversely, when ATF4 expression was knocked down using siRNA in ECV304 cells, it protected the cells from radiation-induced apoptosis. These findings suggest that ATF4 may play a role in radiation-induced cell killing by inhibiting cell proliferation and promoting cell apoptosis. CONCLUSIONS: In this study, we found that radiation up-regulated the expression of ATF4. We used ATF4 knockdown and over-expression systems to show that ATF4 may play a role in radiation-induced cellular apoptosis.

Melatonin attenuates 60 Co γ-ray-induced hematopoietic, immunological and gastrointestinal injuries in C57BL/6 male mice.

Protection of hematopoietic, immunological, and gastrointestinal injuries from deleterious effects of ionizing radiation is prime rational for developing radioprotector. The objective of this study, therefore, was to evaluate the radioprotective potential of melatonin against damaging effects of radiation-induced hematopoietic, immunological, and gastrointestinal injuries in mice. C57BL/6 male mice were intraperitoneally administered with melatonin (50-150 mg/kg) 30 min prior to whole-body radiation exposure of 5 and 7.5 Gy using 60 Co-teletherapy unit. Thirty-day survival against 7.5 Gy was monitored. Melatonin (100 mg/kg) pretreatment showed 100% survival against 7.5 Gy radiation dose. Melatonin pretreatment expanded femoral HPSCs, and inhibited spleenocyte DNA strands breaks and apoptosis in irradiated mice. At this time, it also protected radiation-induced loss of T cell sub-populations in spleen. In addition, melatonin pretreatment enhanced crypts regeneration and increased villi number and length in irradiated mice. Translocation of gut bacteria to spleen, liver and kidney were controlled in irradiated mice pretreated with melatonin. Radiation-induced gastrointestinal DNA strand breaks, lipid peroxidation, and expression of proapoptotic-p53, Bax, and antiapoptotic-Bcl-xL proteins were reversed in melatonin pretreated mice. This increase of Bcl-xL was associated with the decrease of Bax/Bcl-xL ratio. ABTS and DPPH radical assays revealed that melatonin treatment alleviated total antioxidant capacity in hematopoietic and gastrointestinal tissues. Present study demonstrated that melatonin pretreatment was able to prevent hematopoietic, immunological, and gastrointestinal radiation-induced injury, therefore, overcoming lethality in mice. These results suggest potential of melatonin in developing radioprotector for protection of bone marrow, spleen, and gastrointestine in planned radiation exposure scenarios including radiotherapy. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 501-518, 2017.

Impact of photon cross section uncertainties on Monte Carlo-determined depth-dose distributions.

This work studies the impact of systematic uncertainties associated to interaction cross sections on depth dose curves determined by Monte Carlo simulations. The corresponding sensitivity factors are quantified by changing cross sections by a given amount and determining the variation in the dose. The influence of total and partial photon cross sections is addressed. Partial cross sections for Compton and Rayleigh scattering, photo-electric effect, and pair production have been accounted for. The PENELOPE code was used in all simulations. It was found that photon cross section sensitivity factors depend on depth. In addition, they are positive and negative for depths below and above an equilibrium depth, respectively. At this depth, sensitivity factors are null. The equilibrium depths found in this work agree very well with the mean free path of the corresponding incident photon energy. Using the sensitivity factors reported here, it is possible to estimate the impact of photon cross section uncertainties on the uncertainty of Monte Carlo-determined depth dose curves.

Optimisation of radiolysis of Reactive Red 120 dye in aqueous solution using ionising (60)Co gamma radiation by response surface methodology.

In recent years, employing radiation technology is gaining great interest in degradation of industrial effluents. In this work the possibility of using gamma irradiation to degrade Reactive Red 120 (C.I.292775) was explored. The effects of pH, dose of gamma irradiation and concentration of dye were examined and their interaction were also established based on their response. For the analysis and optimisation of variables, three factor three level Box-Wilson face centred central composite design (CCF) was used. Analysis of variance with R(2) = 0.9988, adjusted R(2) = 0.9981 and the adequate precision value of 122.303 indicates that the CCF model can be used. The coefficient of variation (0.54%) indicates the reliability of the model. The dose of gamma irradiation (kGy) and the concentration of dye (mg/L) showed significant effects on the degradation of RR 120, while a difference of 6 to 10% degradation was observed in extending the pH towards the acid or alkali range from pH 7.00. The maximum concentration of dye degraded was observed as 347.509 mg/L at initial pH: 7.0, dose of gamma irradiation: 5.94 kGy and initial concentration of dye: 500 mg/L. This predicted value was found to be in agreement with the experimental value on the optimised conditions.