Celecoxib mitigates genotoxicity induced by ionizing radiation in human blood lymphocytes.

Ionizing radiation causes DNA damage and chromosome abbreviations on normal cells. The radioprotective effect of celecoxib (CLX) was investigated against genotoxicity induced by ionizing radiation in cultured human blood lymphocytes. Peripheral blood samples were collected from human volunteers and were incubated at different concentrations at 1, 5, 10 and 50 µM of CLX for two hours. At each dose point, the whole blood was exposed in vitro to 150 cGy of X-ray, and then the lymphocytes were cultured with mitogenic stimulation to determine the micronucleus frequency in cytokinesis blocked binucleated lymphocytes. Incubation of the whole blood with CLX exhibited a significant decrease in the incidence of micronuclei in lymphocytes induced by ionizing radiation, as compared with similarly irradiated lymphocytes without CLX treatment. The maximum reduction on the frequency of micronuclei was observed at 50 µM of CLX (65% decrease). This data may have an important possible application for the protection of human lymphocytes from the genetic damage induced by ionizing irradiation in human exposed to radiation.

The modulating effect of royal jelly consumption against radiation-induced apoptosis in human peripheral blood leukocytes.

The present work was designed to assess the radioprotective effect of royal jelly (RJ) against radiation-induced apoptosis in human peripheral blood leukocytes. In this study, peripheral blood samples were obtained on days 0, 4, 7, and 14 of the study from six healthy male volunteers taking a 1000 mg RJ capsule orally per day for 14 consecutive days. On each sampling day, all collected whole blood samples were divided into control and irradiated groups which were then exposed to the selected dose of 4 Gy X-ray. Percentage of apoptotic cells (Ap %) was evaluated for all samples immediately after irradiation (Ap0) and also after a 24 h postirradiation incubation at 37°C in 5% CO2 (Ap24) by the use of neutral comet assay. Concerning Ap0, collected data demonstrated that the percentage of apoptotic cells in both control and irradiated groups did not significantly change during the study period. However, with respect to Ap24, the percentage of apoptotic cells in irradiated groups gradually reduced during the experiment, according to which a significant decrease was found after 14 days RJ consumption (P = 0.002). In conclusion, the present study revealed the protective role of 14 days RJ consumption against radiation-induced apoptosis in human peripheral blood leukocytes.

Radiosensitization Effects of a Zataria multiflora Extract on Human Glioblastoma Cells.

BACKGROUND: Although radiotherapy is one of the most effective strategies in the treatment of cancers, it is associated with short and long term side effects on normal tissues. Zataria multiflora Boiss (Laminacea) (ZM) has several biological properties such as antioxidant and anti-inflammation activities.Here we investigated cell killing effects of a hydroalcoholic Zataria multiflora extract on cell death induced by ionizing radiation in a human glioblastoma cell line (A172) and human non-malignant fibroblasts (HFFF2) in vitro. MATERIALS AND METHODS: A172 and HFFF2 cells were treated with a hydroalcoholic extract of dried aerial parts of Zataria multiflora at different concentrations (25, 50, 100, 150 and 200 µg/ml) and then exposed to ionizing radiation (IR). Cell proliferation and DNA fragmentation were evaluated. Thymol content in the extract was analyzed and quantified by HPLC methods. RESULTS: A172 cell proliferation was significantly inhibited by ZM. The percentage cell survival was 91.8 ± 8.57 for cells treated with 200 µg/ml of ZM extract alone while it was 76.0 ± 4.27 and 66.2 ± 8.42 for cells treated with ZM and exposed to IR at doses of 3 Gy and 6Gy, respectively. Radiation-induced apoptosis in A172 cells was significantly increased following treatment with ZM at doses of 200 µg/ml. ZM extract did not exhibit any enhanced cell killing effects and apoptosis caused by IR on HFFF2 cells. CONCLUSIONS: These data show selective radiosensitization effects of ZM in A172 cells apparently due to increased radiation-induced apoptosis.

Assessment of target volume doses in radiotherapy based on the standard and measured calibration curves.

CONTEXT: In radiation treatments, estimation of the dose distribution in the target volume is one of the main components of the treatment planning procedure. To estimate the dose distribution, the information of electron densities is necessary. The standard curves determined by computed tomography (CT) scanner that may be different from that of other oncology centers. In this study, the changes of dose calculation due to the different calibration curves (HU-ρel) were investigated. MATERIALS AND METHODS: Dose values were calculated based on the standard calibration curve that was predefined for the treatment planning system (TPS). The calibration curve was also extracted from the CT images of the phantom, and dose values were calculated based on this curve. The percentage errors of the calculated values were determined. STATISTICAL ANALYSIS USED: The statistical analyses of the mean differences were performed using the Wilcoxon rank-sum test for both of the calibration curves. RESULTS AND DISCUSSION: The results show no significant difference for both of the measured and standard calibration curves (HU-ρel) in 6, 15, and 18 MeV energies. In Wilcoxon ranked sum nonparametric test for independent samples with P<0.05, the equality of monitor units for both of the curves to transfer 200 cGy doses to reference points was resulted. The percentage errors of the calculated values were lower than 2% and 1.5% in 6 and 15 MeV, respectively. CONCLUSION: From the results, it could be concluded that the standard calibration curve could be used in TPS dose calculation accurately.

Radioprotective effect of mefenamic acid against radiation-induced genotoxicity in human lymphocytes.

PURPOSE: Mefenamic acid (MEF) as a non-steroidal anti-inflammatory drug is used as a medication for relieving of pain and inflammation. Radiation-induced inflammation process is involved in DNA damage and cell death. In this study, the radioprotective effect of MEF was investigated against genotoxicity induced by ionizing radiation in human blood lymphocytes. MATERIALS AND METHODS: Peripheral blood samples were collected from human volunteers and incubated with MEF at different concentrations (5, 10, 50, or 100 µM) for two hours. The whole blood was exposed to ionizing radiation at a dose 1.5 Gy. Lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis blocked binucleated lymphocyte. RESULTS: A significant decreasing in the frequency of micronuclei was observed in human lymphocytes irradiated with MEF as compared to irradiated lymphocytes without MEF. The maximum decreasing in frequency of micronuclei was observed at 100 µM of MEF (38% decrease), providing maximal protection against ionizing radiation. CONCLUSION: The radioprotective effect of MEF is probably related to anti-inflammatory property of MEF on human lymphocytes.

Does nitrogen gas bubbled through a low density polymer gel dosimeter solution affect the polymerization process?

BACKGROUND: On account of the lower electron density in the lung tissue, the dose distribution in the lung cannot be verified with the existing polymer gel dosimeters. Thus, the aims of this study are to make a low density polymer gel dosimeter and investigate the effect of nitrogen gas bubbles on the R2 responses and its homogeneity. MATERIALS AND METHODS: Two different types of low density polymer gel dosimeters were prepared according to a composition proposed by De Deene, with some modifications. In the first type, no nitrogen gas was perfused through the gel solution and water. In the second type, to expel the dissolved oxygen, nitrogen gas was perfused through the water and gel solution. The post-irradiation times in the gels were 24 and 5 hours, respectively, with and without perfusion of nitrogen gas through the water and gel solution. RESULTS: In the first type of gel, there was a linear correlation between the doses and R2 responses from 0 to 12 Gy. The fabricated gel had a higher dynamic range than the other low density polymer gel dosimeter; but its background R2 response was higher. In the second type, no difference in R2 response was seen in the dose ranges from 0 to 18 Gy. Both gels had a mass density between 0.35 and 0.45 g.cm(-3) and CT values of about -650 to -750 Hounsfield units. CONCLUSION: It appeared that reactions between gelatin-free radicals and monomers, due to an increase in the gel temperature during rotation in the household mixer, led to a higher R2-background response. In the second type of gel, it seemed that the collapse of the nitrogen bubbles was the main factor that affected the R2-responses.

Differential dose volume histograms of Gamma knife in the presence of inhomogeneities using MRI-polymer gel dosimetry and MC simulation.

Polymer gel dosimeters offer a practical solution to 3D dose verification for conventional radiotherapy as well as intensity-modulated and stereotactic radiotherapy. In this study, EGSnrc calculated and PAGAT polymer gel dosimeter measured dose volume histograms (DVHs) for single-shot irradiations of the Gamma Knife (GK) unit were used to investigate the effects of the presence of inhomogeneities on 3D dose distribution. The head phantom was a custom-built 16 cm diameter Plexiglas sphere. Inside the phantom, there is a cubic cutout for inserting the gel vials and another cutout for inserting the inhomogeneities. Following irradiation with the GK unit, the polymer gel phantoms were scanned with a 1.5 T MRI scanner. Comparing the results of measurement in homogeneous and heterogeneous phantoms revealed that inserting inhomogeneities inside the homogeneous phantom did not cause considerable disturbances on dose distribution in irradiation with 8 mm collimator within low isodose levels (< 50%), which is essential for the dose sparing of sensitive structures. The results of simulation for homogeneous and inhomogeneous phantoms in irradiation with 18 mm collimator of the GK unit showed 23.24% difference in DVH within 90%-100% relative isodose level and also revealed that a significant part of the target (28.56%) received relative doses higher than the maximum dose, which exceeds the acceptance criterion (5%). Based on these results it is concluded that the presence of inhomogeneities inside the phantom can cause considerable errors in dose calculation within high isodose levels with respect to LGP prediction which assumes that the target is a homogeneous material. Moreover, it is demonstrated that the applied MC code is an accurate and stand-alone tool for 3D evaluation of dose distribution in irradiation with the GK unit, which can provide important, 3D plan evaluation criteria used in clinical practice.

Performance evaluation of MRI-based PAGAT polymer gel dosimeter in an inhomogeneous phantom using EGSnrc code on a Co-60 machine.

Relative isodose curves were obtained using PAGAT gel dosimeter on homogeneous and inhomogeneous phantoms. Distance-to-agreement (DTA) was calculated between simulated and measured values for both the homogeneous and inhomogeneous phantoms. All DTAs except one passed the acceptance criterion (+/-5 dose variation for selected isodose levels). Results of this study also showed the ability of the Monte Carlo modeling to provide accurate dosimetry, and revealed that the dose response of PAGAT polymer gel is dependent on the method of fabrication.