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To analyze the biological effects of radiation, it is important that the conditions of in vitro experiments match closely with those of in vivo experiments. In this study, we constructed an irradiation system to conduct irradiation experiments under conditions similar to those of in vivo experiments. The Dongnam Institute of Radiological and Medial Sciences has a gamma irradiator including 60Co radioisotope for research purposes and accreditation for standard calibration of the ion chamber. The temperature of the water phantom was maintained the same as that of the normal human body, and the physical dosimetry was carried out accurately using the ion chamber with traceability. We report the measurement of lateral profiles, depth profiles, and absorbed dose rate in water, Dw, at the irradiation location of the blood samples using a farmer-type ion chamber. We simulated the source, collimator, irradiator, phantom, and extra structure of the gamma irradiation system using the Monte Carlo code and compared the simulated and the experimental results. The experimentally and theoretically evaluated dose rates were 0.2975 ± 0.0055 Gymin–1 (at coverage factor k = 2) and 0.2978 ± 0.0052 Gymin–1 (at coverage factor k = 2) at source-to-surface distance of 100 cm and 5 gcm–2 depth in the water phantom, respectively. Blood irradiation will be conducted in vitro, under conditions similar to in vivo conditions, to provide the dose-response curve based on dosimetry with traceability.

Evaluating the radiation dose of target organs of a laboratory mouse requires a glass dosimeter to be surgically inserted at the irradiated location. However, precisely inserting the glass dosimeter at the same location in different mice is rarely achieved, reducing the reliability of the measured radiation dose. To address this limitation, 3-D mouse phantom was developed using computed tomography scanning and 3-D printing technology. The radiation dose of target organs was assessed using four mouse models: laboratory mouse, 3-D mouse phantom, Monte Carlo N-Particle (MCNP) 3-D phantom, and MCNP simulation. In all the experiments, the brain, heart, lungs, and abdomen were irradiated with 100 mGy of measured air kerma at a 6 mGyh–1 air kerma rate. A small volume glass dosimeter was inserted into the mouse models to assess the radiation dose, and the reliability of the glass dosimeter reading system was evaluated using the dose-response curves. The dose values of the laboratory mouse and 3-D-printed mouse phantom were found to differ by up to 3.3 %. This study provides a method to accurately measure the radiation dose to target organs, enhancing the reliability of pre-experiments.

Networking with other biodosimetry laboratories is necessary to assess the radiation exposure of many individuals in large-scale radiological accidents. The Korea biodosimetry network, K-BioDos, prepared harmonized scoring guidelines for dicentric chromosome assay to obtain homogeneous results within the network and investigated the efficiency of the guidelines. Three laboratories in K-BioDos harmonized the scoring guidelines for dicentric chromosome assay. The results of scoring dicentric chromosomes using the harmonized scoring guidelines were compared with the laboratories' results using their own methods. Feedback was collected from the scorers following the three intercomparison exercises in 3 consecutive years. K-BioDos members showed comparable capacity to score dicentrics in the three exercises. However, the results of the K-BioDos guidelines showed no significant improvement over those of the scorers' own methods. According to the scorers, our harmonized guidelines led to more rejected metaphases and ultimately decreased the number of scorable metaphases compared with their own methods. Moreover, the scoring time was sometimes longer with the K-BioDos protocol because some scorers were not yet familiar with the guidelines, though most scorers reported that the time decreased or was unchanged. These challenges may cause low adherence to the guidelines. Most scorers expressed willingness to use the guidelines to select scorable metaphases or identify dicentrics for other biodosimetry works, whereas one did not want to use it due to the difference from their calibration curves. We identified potential resistance to following the harmonized guidelines and received requests for more detailed methods. Our findings suggest that the harmonized criteria should be continually updated, and education and training should be provided for all scorers. These changes could allow members within the biodosimetry network to successfully collaborate and support each other in large-scale radiological accidents. [ABSTRACT FROM AUTHOR]

Although there are several types of radiation exposure, it is debated whether low-dose-rate (LDR) irradiation (IR) affects the body. Since the small intestine is a radiation-sensitive organ, the present study aimed to evaluate how it changes when exposed to LDR IR and identify the genes sensitive to these doses. After undergoing LDR (6.0 mGy/h) γ radiation exposure, intestinal RNA from BALB/c mice was extracted 1 and 24 h later. Mouse whole genome microarrays were used to explore radiation-induced transcriptional alterations. Reverse transcription-quantitative (RT-q) PCR was used to examine time- and dose-dependent radiation responses. The histopathological status of the jejunum in the radiated mouse was not changed by 10 mGy of LDR IR; however, 23 genes were upregulated in response to LDR IR of the jejunum in mice after 1 and 24 h of exposure. Upregulated genes were selected to validate the results of the RNA sequencing analysis for RT-qPCR detection and results showed that only Na+/K+ transporting subunit α4, glucose-6-phosphatase catalytic subunit 2 (G6PC2), mucin 6 (MUC6) and transient receptor potential cation channel subfamily V member 6 levels significantly increased after 24 h of LDR IR. Furthermore, G6PC2 and MUC6 were notable genes induced by LDR IR exposure according to protein expression via western blot analysis. The mRNA levels of G6PC2 and MUC6 were significantly elevated within 24 h under three conditions: i) Exposure to LDR IR, ii) repeated exposure to LDR IR and iii) exposure to LDR IR in the presence of inflammatory bowel disease. These results could contribute to an improved understanding of immediate radiation reactions and biomarker development to identify radiation-susceptible individuals before histopathological changes become noticeable. However, further investigation into the specific mechanisms involving G6PC2 and MUC6 is required to accomplish this. [ABSTRACT FROM AUTHOR]

Hypoxia is associated with resistance to anticancer therapies. Additionally, it is involved in the immune evasion of cancer cells by inducing an immunosuppressive microenvironment. However, the role of hypoxia in modulating the immunogenicity of cancer cells remains unknown. Hypoxia is known to induce endoplasmic reticulum (ER) stress, which serves a key role in inducing the cell surface exposure of calreticulin, a marker of immunogenic cell death. The present study investigated whether hypoxia influenced the immunogenicity of cancer cells using FACS, western blot analysis and syngenic mouse tumor model. The results revealed that hypoxia induced the cell surface exposure of calreticulin in human and mouse breast cancer cell lines depending on ER stress. Enhanced cell surface exposure of calreticulin induced by hypoxia resulted in an increase in anticancer immunity in a mouse model, which suggested that hypoxia induced immunogenic cell death. Notably, hypoxia did not significantly modulate the cell surface exposure of CD47, an antagonist of calreticulin function in cancer immunogenicity. These results suggest that hypoxia may enhance the immunogenicity of cancer cells themselves, in addition to its role in inducing an immunosuppressive cancer microenvironment. [ABSTRACT FROM AUTHOR]