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Background: Radiation-induced heart injury can lead to increased risk of heart failure, attack, and ischemia. Some studies proposed IL-4 and IL-13 as two important cytokines that are involved in late effects of ionizing radiation. On the other hand, these cytokines may, through upregulation of Duox1 and Duox2, induce chronic oxidative stress, inflammation, and fibrosis. In this study, we evaluated the upregulation of Duox1 and Duox2 pathways in hearts following chest irradiation in rats and then detected possible attenuation of them by melatonin. Materials and Methods: Twenty male Wistar rats were divided into four groups: (1) control, (2) melatonin treated (100 mg/kg), (3) radiation (15 Gy gamma rays), (4) melatonin treated before irradiation. All rats were sacrificed after 10 weeks and their heart tissues collected for real-time PCR (RT-PCR), ELISA detection of IL-4 and IL-13, as well as histopathological evaluation of macrophages and lymphocytes infiltration. Results: Results showed an upregulation of IL-4, IL4ra1, Duox1, and Duox2. The biggest changes were for IL4ra1 and Duox1. Treatment with melatonin before irradiation could attenuate the upregulation of all genes. Melatonin also caused a reduction in IL-4 as well as reverse infiltration of inflammatory cells. Conclusion: Duox1 and Duox2 may be involved in the late effects of radiation-induced heart injury. Also, via attenuation of these genes, melatonin can offer protection against the toxic effects of radiation on the heart.

The severe toxicity in compound of polymer gel dosimeters has been reported as one of their major limitations for utilization in clinical applications. Recently, PASSAG polymer gel dosimeter has been introduced as a safe polymer gel dosimeter. Despite the excellent dosimetric results reported for this gel dosimeter, its R2-dose sensitivity is relatively low. Therefore, the present study is aimed to improve the sensitivity of PASSAG gel dosimeter by adding urea to its structure. Moreover, it was tried to obtain the optimal amount of urea for the new gel dosimeter. After preparation of the PASSAG-U (PASSAG and Urea) gel dosimeters, they were irradiated using 6 MV photon energy and their responses were read by a 1.5 T MRI scanner. Then, the R2-dose response and the R2-dose sensitivity of the PASSAG-U gel dosimeters with various percentages of the urea were assessed at a 0–10 Gy dose range, various scanning temperatures (15–24 °C), and post irradiation times (1–30 days). The radiological properties of PASSAG-U gel dosimeters confirmed soft tissue and water equivalence of the new gel dosimeters. Compared to the PASSAG gel dosimeter, the R2-dose sensitivities of PASSAG-U gel dosimeters with 1%, 3%, and 5% urea were improved by 12.14%, 25.15%, and 27.90%, respectively. Although the addition of urea improves the R2-dose sensitivity of the gel dosimeter, it leads to the degradation of dose resolution (especially for 5% urea). Moreover, the dosimetric evaluation of characteristics related to the PASSAG-U gel dosimeters with various urea concentrations resulted to following conclusions: 1) the optimal amount of urea was determined 3%; 2) there was a stability in the R2 values for 18–22 °C scanning temperatures; 3) there was a temporal stability at the response of PASSAG-U gel dosimeters from 14 to 30 days after irradiation; 4) the R2-dose sensitivity of PASSAG-U gel dosimeters varied over post irradiation time.

Background : There is no geometrical nucleotide resolution model which can be used in numerical simulations of the interaction between radiation and supercoiled mt-DNA to perform realistic evaluations of DNA–free radical reactions. Objectives: A new geometrical model of mitochondrial DNA (mt-DNA) is developed in Geant 4-DNA to investigate the radiation-induced damage on mt-DNA. The presented application can be used to modify both geometrical parameters and structural elements, and to evaluate the damage induced on the mt-DNA molecule by ionizing particles. Methods : Our model covers the organisation of a supercoiled human mitochondrial genetic system. The current model includes all 16,659 base pairs of human mitochondrial DNA. This new mtDNA model has been preliminarily tested in this work by determining SSB and DSB DNA damage yields and site-hit probabilities due to the impact of proton particles. Results : Determination of single-strand (SSBs) and double-strand breaks (DSBs) is designed using the locations of all hit sites. Estimation of single-strand breaks and double strand breaks yielded similar results with the increment of incident particle LET. The output results contain the information about the energy transfers in the backbone region of DNA double helix. Conclusions : Considerations seem to be consistent with the corresponding experimental determinations. This application can be used for the investigation of radiation-induced damage to the mitochondrial genome and in any problems that require a supercoiled geometrical model. This work is going to be extended to circular conformation in a parallel project in the near future.

Objective: The Lung is one of the most radiosensitive organs of the body. The infiltration of macrophages and lymphocytes into the lung is mediated via the stimulation of T-helper 2 cytokines such as IL-4 and IL-13, which play a key role in the development of fibrosis. It is likely that these cytokines induce chronic oxidative damage and inflammation through the upregulation of Duox1 and Duox2, which can increase the risk of late effects of ionizing radiation (IR) such as fibrosis and carcinogenesis. In the present study, we aimed to evaluate the possible increase of IL-4 and IL-13 levels, as well as their downstream genes such as IL4ra1, IL13ra2, Duox1, and Duox2. Materials and Methods: In this experimental animal study, male rats were divided into 4 groups: i. Control, ii. Melatonintreated, iii. Radiation, and iv. Melatonin (100 mg/kg) plus radiation. Rats were irradiated with 15 Gy 60Co gamma rays and then sacrificed after 67 days. The expressions of IL4ra1, IL13ra2, Duox1, and Duox2, as well as the levels of IL-4 and IL-13, were evaluated. The histopathological changes such as the infiltration of inflammatory cells, edema, and fibrosis were also examined. Moreover, the protective effect of melatonin on these parameters was also determined. Results: Results showed a 1.5-fold increase in the level of IL-4, a 5-fold increase in the expression of IL4ra1, and a 3-fold increase in the expressions of Duox1 and Duox2. However, results showed no change for IL-13 and no detectable expression of IL13ra2. This was associated with increased infiltration of macrophages, lymphocytes, and mast cells. Melatonin treatment before irradiation completely reversed these changes. Conclusion: This study has shown the upregulation of IL-4-IL4ra1-Duox2 signaling pathway following lung irradiation. It is possible that melatonin protects against IR-induced lung injury via the downregulation of this pathway and attenuation of inflammatory cells infiltration.

Background The aim of this study was to develop a nucleotide geometrical model of the circular mitochondrial DNA (mt-DNA) structure using Geant4-DNA toolkit to predict the radiation-induced damages such as single-strand breaks (SSB), double-strand breaks (DSB), and some other physical parameters. Methods Our model covers the organization of a circular human mt genetic system. The current model includes all 16,659 base pairs of human mt-DNA. This new mt-DNA model has been preliminarily tested in this work by determining SSB and DSB DNA damage yields and site-hit probabilities due to the impact of proton particles. The accuracy of the geometry was determined by three-dimensional visualization in various ring element numbers. The hit locations were determined with respect to a reference coordinate system, and the corresponding base pairs were stored in the ROOT output file. Results The coordinate determination according to the algorithm was consistent with the expected results. The output results contain the information about the energy transfers in the backbone region of the DNA double helix. The output file was analyzed by root analyzing tools. Estimation of SSBs and DSBs yielded similar results with the increment of incident particle linear energy transfer. In addition, these values seem to be consistent with the corresponding experimental determinations. Conclusions This model can be used in numerical simulations of mt-DNA radiation interactions to perform realistic evaluations of DNA-free radical reactions. This work will be extended to supercoiled conformation in the near future.

In this work, the general purpose Monte Carlo N-particle radiation transport computer code (MCNP-4C) was used for the simulation of X-ray spectra in diagnostic radiology. The electron's path in the target was followed until its energy was reduced to 10 keV. A user-friendly interface named ‘diagnostic X-ray spectra by Monte Carlo simulation (DXRaySMCS)’ was developed to facilitate the application of MCNP-4C code for diagnostic radiology spectrum prediction. The program provides a user-friendly interface for: (i) modifying the MCNP input file, (ii) launching the MCNP program to simulate electron and photon transport and (iii) processing the MCNP output file to yield a summary of the results (relative photon number per energy bin). In this article, the development and characteristics of DXRaySMCS are outlined. As part of the validation process, output spectra for 46 diagnostic radiology system settings produced by DXRaySMCS were compared with the corresponding IPEM78. Generally, there is a good agreement between the two sets of spectra. No statistically significant differences have been observed between IPEM78 reported spectra and the simulated spectra generated in this study.