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Background: High-dose radiation altering the genetic material in patients' bone marrow cells can lead to hematopoietic radiation syndrome. Accordingly, the presence of radiation protections agents is critical to preventing these adverse effects. Objective: This study aimed to evaluate the radioprotection of the exclusive or combination effect of resveratrol and crocin extracts at various concentrations on irradiated human lymphocytes. Material and Methods: In this experimental study, the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was used to evaluate the cell viability in pre-treatment with resveratrol, crocin, or a combination of both, using a concentration range of 5 to 4800 μM / ml in 24 h. The chromosomal aberration test was employed to determine the aberration frequency in 48 h. This study was performed on human peripheral blood lymphocytes treated with 2 Gy radiation and reliability of measurements performed by the triplicate repeat. Results: MTT results showed that the groups treated with either resveratrol or crocin at concentrations of 5 to 4800 µM had no significant reduction in cell viability. The cytogenetic analysis of irradiated lymphocytes with 2 Gy X-rays revealed a reduction in the frequency of dicentric chromosomes in all treated groups in contrast with the control group. The most significant reduction occurred in those treated with a single agent at the concentration of 100 µM and a combined drug at the concentration of 50 µM. Conclusion: The combination of resveratrol and crocin is considered a potential radioprotector and prophylactic for patients before radiation therapy. [ABSTRACT FROM AUTHOR]

Objective: Spinal cord injury (SCI) causes motor deficits, urinary incontinence, and neuropathic pain. This study was designed to optimize a photobiomodulation therapy (PBMT) protocol using a continuous wave (CW) 660 nm laser in rats with SCI. Specifically, the number of days of irradiation and the daily dose of PBMT were investigated. Methods: The study was performed in two steps. In the first step, a comparison between the effects of PBMT (45 sec) daily for 2 and 4 weeks on pain and movement [Basso, Beattie, and Brenham (BBB) score] was made. In the second step, a comparison between different durations of irradiation (27, 45, 90, and 117 sec) was performed. PBMT used a 100mW laser delivered to 9 points on and around the lesion site. Oxidative stress, fibroblast invasion, and time to achieve spontaneous urination were also assessed. Results: The improvement in movement and pain stopped with discontinuation of radiation at week 2 and fibroblast invasion resumed. No improvement was seen in movement and pain in the group receiving PBMT for 27 sec compared with the groups receiving higher doses of laser radiation. Animals receiving 117 sec of photobiomodulation showed a higher BBB score even in the first 3 days. Conclusions: The number of days is an important factor for improving mobility; however, the daily dose of radiation is more important for pain relief. [ABSTRACT FROM AUTHOR]

Background: Melanoma is categorized as one of the most malignant, severe, and lethal cancers of the skin. Regarding the lack of efficiency of conventional therapies for most patients, novel therapeutic strategies are strongly required. Objective: The current study aimed to assess the impact of AZD6738- an ATR kinase inhibitor- in combination with 6 MV X-ray on the human melanoma cell line (A375). Material and Methods: In this experimental study, cells were treated with different concentrations of AZD6738 for 24 and 48 h in the presence and absence of radiation (2 Gy, 4 Gy, and 6 Gy). The cell viability and cell proliferation assay were examined in both experimental and control groups by MTT and colony formation techniques, respectively. Results: The results indicated that by increasing the concentration of AZD6738, the cell viability was markedly diminished in all treatment groups. As expected, the cell viability of the cells treated with AZD6738 and radiation was significantly lower than the group treated with AZD6738 alone. Besides, the combinatory treatment significantly decreased cell proliferation in the melanoma cell line. The combination of AZD6738 with radiation resulted in a significant increase in cytotoxicity by a 50% increase in cell death when used at concentrations of 0.3 µM, 1 µM, 1.51 µM, and 1.61 µM, respectively. Conclusion: The combination of AZD6738 with radiation possesses a synergistic effect on the reduction of the cell viability and proliferation of melanoma cells. This present study provides insight into the impact of Ataxia Telangiectasia and Rad3-related kinase (ATR) inhibition on the potential role of this kinase in the suppression of melanoma cell proliferation. [ABSTRACT FROM AUTHOR]

Objective: Glioblastoma (GBM) is one of the devastating types of primary brain tumors with a negligible response to standard therapy. Repurposing drugs, such as disulfiram (DSF) and metformin (Met) have shown antitumor properties in different cell lines, including GBM. In the present study, we focused on the combinatory effect of Met and DSF-Cu on the induction of apoptosis in U87-MG cells exposed to 6-MV X-ray beams. Materials and Methods: In this experimental study, the MTT assay was performed to evaluate the cytotoxicity of each drug, along with the combinatory use of both. After irradiation, the apoptotic cells were assessed using the flow cytometry, western blot, and real-time polymerase chain reaction (RT-PCR) to analyze the expression of some cell death markers such as BAX and BCL-2. Results: The synergistic application of both Met and DSF had cytotoxic impacts on the U87-MG cell line and made them sensitized to irradiation. The combinatory usage of both drugs significantly decreased the cells growth, induced apoptosis, and caused the upregulation of BAX, P53, CASPASE-3, and it also markedly downregulated the expression of the anti-apoptotic protein BCL-2 at the gene and protein levels. Conclusion: It seems that the synergistic application of both Met and DSF with the support of irradiation can remarkably restrict the growth of the U87-MG cell line. This may trigger apoptosis via the stimulation of the intrinsic pathway. The combinatory use of Met and DSF in the presence of irradiation could be applied for patients afflicted with GBM. [ABSTRACT FROM AUTHOR]

Objective: Melanoma is the most malignant and severe type of skin cancer. It is a tumor with a high risk of metastasis and resistant to conventional treatment methods (surgery, radiotherapy, and chemotherapy). β-elemene is the most active constituent of Curcuma wenyujin which is a non-cytotoxic antitumor drug, proved to be effective in different types of cancers. The study aimed to investigate the therapeutic effects of β-elemene in combination with radiotherapy on A375 human melanoma. Materials and Methods: In this experimental study, human melanoma cells were grown in the monolayer culture model. The procedure of the treatment was performed by the addition of different concentrations of β-elemene to the cells. Then, the cells were exposed to 2 and 4 Gy X-ray in different incubation times (24, 48, and 72 hours). The MTT assay was used for the determination of the cell viability. To study the rate of apoptosis response to treatments, the Annexin V/PI assay was carried out. Results: The results of the MTT assay showed β-elemene reduced the cell proliferation in dose- and time-dependent manners in cells exposed to radiation. Flow cytometry analysis indicated that β-elemene was effective in the induction of apoptosis. Furthermore, the combination treatment with radiation remarkably decreased the cells proliferation ability and also enhanced apoptosis. For example, cell viability in a group exposed to 40 μg/ml of β-elemene was 80%, but combination treatment with 6 MV X beam at a dose of 2 Gy reduced the viability to 61%. Conclusion: Our results showed that β-elemene reduced the proliferation of human melanoma cancer cell through apoptosis. Also, the results demonstrated that the radio sensitivity of A375 cell line was significantly enhanced by β-elemene. The findings of this study indicated the efficiency of β-elemene in treating melanoma cells and the necessity for further research in this field. [ABSTRACT FROM AUTHOR]

Objective: To explore the cumulative genotoxic damage to glioblastoma (GBM) cells, grown as multicellular spheroids, following exposure to 6 MV X-rays (2 Gy, 22 Gy) with or without, 2- methoxy estradiol (2ME2), iododeoxyuridine (IUDR) or topotecan (TPT), using the Picogreen assay. Materials and Methods: The U87MG cells cultured as spheroids were treated with 6 MV X-ray using linear accelerator. Specimens were divided intofive groups and irradiated using X-ray giving the dose of 2 Gy after sequentially incubated with one of the following three drug combinations: TPT, 2-ME2/TPT, IUDR/TPT or 2ME2/IUDR/ TPT. One specimen was used as the irradiated only sample (R). The last group was also irradiated with total dose of 22 Gy (each time 2 Gy) of 6 MV X-ray in 11 fractions and treated for three times. DNA damage was evaluated using the Picogreen method in the experimental study. Results: R/TPT treated group had more DNA damage [double strand break (DSB)/single strand break (SSB)] compared with the untreated group (P<0.05). Moreover the R/ TPT group treated with 2ME2 followed by IUDR had maximum DNA damage in spheroid GBM indicating an augmented genotoxicity in the cells. The DNA damage was induced after seven fractionated irradiation and two sequential treatments with 2ME2/IUDR/TPT. To ensure accuracy of the slope of dose response curve the fractionated radiation was calculated as 7.36 Gy with respect to α/β ratio based on biologically effective dose (BED) formulae. Conclusion: Cells treated with 2ME2/IUDR showed more sensitivity to radiation and accumulative DNA damage. DNA damage was significantly increased when GBM cells treated with TPT ceased at S phase due to the inhibition of topoisomerase enzyme and phosphorylation of Chk1 enzyme. These results suggest that R/TPTtreated cells increase sensitivity to 2ME2 and IUDR especially when they are used together. Therefore, due to an increase in the level of DNA damage (SSB vs. DSB) and impairment of DNA repair machinery, more cell death will occur. This in turn may improve the treatment of GBM. [ABSTRACT FROM AUTHOR]

Objective: Glioblastoma multiforme (GBM), one of the most common and aggressive malignant brain tumors, is highly resistant to radiotherapy. Numerous approaches have been pursued to find new radiosensitizers. We used a picogreen and colonogenic assay to appraise the DNA damage and cell death in a spheroid culture of GBM cells caused by iodine-131 (I-131) beta radiation in the presence of topotecan (TPT). Materials and Methods: U87MG cells were cultured as spheroids with approximate diameters of 300 μm. Cells were treated with beta radiation of I-131 (at a dose of 2 Gy) and/ or TPT (1 μg/ml for 2 hours). The numbers of cells that survived were compared with untreated cells using a colonogenic assay. In addition, we evaluated possible DNA damages by the picogreen method. The relation between DNA damage and cell death was assessed in the experimental study of groups. Results: The findings showed that survival fraction (SF) in the I-131+TPT group (39%) was considerably less than the I-131 group (58.92%; p<0.05). The number of single strand breaks (SSB) and double strand breaks (DSB), in the DNA of U87MG cells treated with beta radiation of I-131 and TPT (I-131+TPT) significantly increased compared to cells treated with only I-131 or TPT (p<0.05). The amount of SSB repair was more than DSB repair (p<0.05). The relationship between cell death and DNA damage was close (r=0.6) and significant (p<0.05) in the irradiated and treated groups. Also the maximum rate of DNA repair occurred 24 hours after the treatments. A significant difference was not observed on other days of the restoration. Conclusion: The findings in the present study indicated that TPT can sensitize U87MG cells to radiation and increase DNA damages. Potentially, TPT can cause an increase in damage from DSB and SSB by its inhibitory effects on topoisomerase enzyme and the cell cycle. The increased complex damages following the use of a genotoxic agent and beta I-131 radiation, causes a significant increase the cell death because of the difficult repair process. By assessing the relationship between DNA damage and cell death, the picogreen method can be useful in predicting colonogenic assay. Consequently, it is suggested that co-treatment with I-131 beta radiation and TPT can improve GBM treatment. [ABSTRACT FROM AUTHOR]

Objective: In radiation treatment, the irradiation which is effective enough to control the tumors far exceeds normal-tissues tolerance. Thus to avoid such unfavourable outcomes, some methods sensitizing the tumor cells to radiation are used. Iododeoxyuridine (IUdR) is a halogenated thymidine analogue that known to be effective as a radiosensitizer in human cancer therapy. Improving the potential efficacy of radiation therapy after combining to hyperthermia depends on the magnitude of the differential sensitization of the hyperthermic effects or on the differential cytotoxicity of the radiation effects on the tumor cells. In this study, we evaluated the combined effects of IUdR, hyperthermia and gamma rays of 60Co on human glioblastoma spheroids culture. Materials and Methods: In this experimental study,the cultured spheroids with 100μm diameter were treated by 1 μM IUdR, 43°C hyperthermia for an hour and 2 Gy gamma rays, respectively. The DNA damages induced in cells were compared using alkaline comet assay method, and dosimetry was then performed by TLD-100. Comet scores were calculated as mean ± standard error of mean (SEM) using one-way ANOVA. Results:Comparison of DNA damages induced by IUdR and hyperthermia + gamma treatment showed 2.67- and 1.92-fold enhancement, respectively, as compared to the damages induced by radiation alone or radiation combined IUdR. Dosimetry results showed the accurate dose delivered to cells. Conclusion: Analysis of the comet tail moments of spheroids showed that the radiation treatments combined with hyperthermia and IUdR caused significant radiosensitization when compared to related results of irradiation alone or of irradiation with IUdR. These results suggest a potential clinical advantage of combining radiation with hyperthermia and indicate effectiveness of hyperthermia treatment in inducing cytotoxicity of tumor cells. [ABSTRACT FROM AUTHOR]

Objective: To assess relative biological effectiveness (RBE) of 131I radiation relative to 60Co gamma rays in glioblastoma spheroid cells. Materials and Methods: In this experimental study, glioblastoma spheroid cells were exposed to 131I radiation and 60Co gamma rays. Radiation induced DNA damage was evaluated by alkaline comet assay. Samples of spheroid cells were treated by radiation from 131I for four different periods of time to find the dose-response equation. Spheroid cells were also exposed by 200 cGy of 60Co gamma rays as reference radiation to induce DNA damage as endpoint. Results: Resulted RBE of 131I radiation relative to 60Co gamma rays in 100 μm giloblastoma spheroid cells was equal to 1.16. Conclusion: The finding of this study suggests that 131I photons and electrons can be more effective than 60Co gamma rays to produce DNA damage in glioblastoma spheroid cells. [ABSTRACT FROM AUTHOR]

Background: Today, a CT scan examination play an important role in disease diagnosis and thus allocates a significant dose of medical X-ray examinations. One of the important principles in the use of ionizing radiations is to observe radiation protection principles. Evaluating patient's absorbed dose and implementing the strategies for reducing dose are prior in safety issues. To achieve this purpose, sufficient studies should be performed in this regard. Therefore, patient's absorbed dose and the factors affecting have been studied in this research. This study aims to present and develop an acceptable level of absorbed dose in CT scan examinations. Methods: Diagnostic reference dose level in the adult age group (older than 15 years) has been studied in eleven CT scan centers in Tehran. For this purpose, CT scan examinations prevalent in above-mentioned centers were chosen and Weighted Computed Tomography dose index (CTDIw) and dose length product (DLP) parameters were studied. Standard phantoms with 16 and 32 diameters of Polymethylmethacrylate (PMMA) origin have been used in the centers for CT scan calibration process. CTDIw third quartile has been considered as the diagnostic reference dose level (DRL). Results: Rate of diagnostic reference dose in the adult age group (older than 15 years) for the head, sinus, lungs, abdomen and pelvis are 50.87, 38.27, 8.05 and 9.11 mg, respectively. Dose measurements made in this survey have been used to set up local DRLs and can be used as a template for national DRLs. Conclusion: Value of diagnostic reference dose for the head examinations is more than the other parts and diagnostic reference dose in Tehran city in the Adult age group and the protocols compared is less than national reference dose. [ABSTRACT FROM AUTHOR]

Objective: The passage of ionizing radiation in living cells creates clusters of damaged nucleotides in DNA. In this study, DNA strand breaks induced by the beta particle of iodine-131 (1-131), have been determined experimentally and compared to Monte Carlo simulation results as a theoretical method of determining131l damage. Materials and Methods: In this experimental study, in order to create single strand breaks (SSB) and double strand breaks (DSB) in the DNA, glioblastoma (GBM) cells were exposed to 10 mCi 1-131, at a dose of 2 Gy. Damage of irradiated cells were evaluated quantitatively by the Fast Micromethod assay. The energy spectrum of electrons released in cells were obtained by the macroscopic Monte Carlo code (MCNP4c) and used as an input of the micro Monte Carlo code (MCDS). The percent of damage induced in cells was analyzed by Mann-Whitney test. Results: A significant reduction (p

Objective: In this study, we investigated the combined effect of 2-Methoxyestradiol (2ME2) and 60Co on the cytogenetic damage of iododeoxyuridine (IUdR) in the spheroid model of U87MG glioblastoma cancer cell lines by alkaline comet assay. Materials and Methods: U87MG cells were cultured as spheroids with diameters of 350 μm. As control, the spheroids of one plate were not treated. Other cultures were pretreated with 2ME2 (250 μM) for one volume doubling time (1 VDT). After this time, the subsequent treatments were performed according to the following groups: 1. Vehicle (this sample was not treated in the 2nd VDT) 2. Treated with 2ME2 (250 μM) for 1 VDT 3. Treated simultaneously with 2ME2 (250 μM) and IUdR (1 μM) for 1 VDT 4. Treated with 2ME2 (250 μM) for 1 VDT then irradiated with 60Co (2 Gy) 5. Treated simultaneously with 2ME2 (250 μM) and IUdR (1 μM) for 1 VDT then irradiated with 60Co (2 Gy) Then the DNA damage was evaluated using the alkaline comet assay method. Results: The results showed that 2ME2 in combination with gamma irradiation of 60Co significantly (p<0.001) increased the DNA damage by IUdR as compared to the control group. Thus the combination of these two agents increased the cytogenetic effects of IUdR in the spheroid culture model of U87MG glioblastoma cell lines. Conclusion: By inhibiting the HIF-1α protein and preventing the G0 phase arrest, 2ME2 causes an increased progression into S phase and increases the IUdR absorption. Then the DNA damage in the spheroid cells increases as the uptake of IUdR is increased. These results suggest that the combined use of 2ME2 and 60Co can increase the radio- sensitization effect of IUdR. [ABSTRACT FROM AUTHOR]

Objective: To assess relative biological effectiveness (RBE) of (131)I radiation relative to (60)Co gamma rays in glioblastoma spheroid cells., Materials and Methods: : In this experimental study, glioblastoma spheroid cells were exposed to (131)I radiation and (60)Co gamma rays. Radiation induced DNA damage was evaluated by alkaline comet assay. Samples of spheroid cells were treated by radiation from (131)I for four different periods of time to find the dose-response equation. Spheroid cells were also exposed by 200 cGy of (60)Co gamma rays as reference radiation to induce DNA damage as endpoint., Results: Resulted RBE of (131)I radiation relative to (60)Co gamma rays in 100 µm giloblastoma spheroid cells was equal to 1.16., Conclusion: The finding of this study suggests that (131)I photons and electrons can be more effective than (60)Co gamma rays to produce DNA damage in glioblastoma spheroid cells.

Objective: In this study, we investigated the combined effect of 2-Methoxyestradiol (2ME2) and (60)Co on the cytogenetic damage of iododeoxyuridine (IUdR) in the spheroid model of U87MG glioblastoma cancer cell lines by alkaline comet assay., Materials and Methods: U87MG cells were cultured as spheroids with diameters of 350 µm. As control, the spheroids of one plate were not treated. Other cultures were pretreated with 2ME2 (250 µM) for one volume doubling time (1 VDT). After this time, the subsequent treatments were performed according to the following groups: Vehicle (this sample was not treated in the 2(nd) VDT) Treated with 2ME2 (250 µM) for 1 VDT Treated simultaneously with 2ME2 (250 µM) and IUdR (1 µM) for 1 VDT Treated with 2ME2 (250 µM) for 1 VDT then irradiated with (60)Co (2 Gy) Treated simultaneously with 2ME2 (250 µM) and IUdR (1 µM) for 1 VDT then irradiated with (60)Co (2 Gy) Then the DNA damage was evaluated using the alkaline comet assay method., Results: The results showed that 2ME2 in combination with gamma irradiation of (60)Co significantly (p<0.001) increased the DNA damage by IUdR as compared to the control group. Thus the combination of these two agents increased the cytogenetic effects of IUdR in the spheroid culture model of U87MG glioblastoma cell lines., Conclusion: By inhibiting the HIF-1α protein and preventing the G0 phase arrest, 2ME2 causes an increased progression into S phase and increases the IUdR absorption. Then the DNA damage in the spheroid cells increases as the uptake of IUdR is increased. These results suggest that the combined use of 2ME2 and (60)Co can increase the radiosensitization effect of IUdR.