Elucidation of gastrointestinal dysfunction in response to irradiation using metabolomics.

Gastrointestinal toxicity is frequently observed secondary to accidental or therapeutic radiation exposure. However, the variation in the intestinal metabolites after abdominal radiation exposure remains ambiguous. In the present study, C57BL/6 mice were exposed to 0, 2, and 20 Gy irradiation dose. The Head and chest of each mouse were covered with a lead shield before x-ray irradiation. 24 h post-irradiation treatment, intestinal tissue of each mouse was excised and prepared for metabolites measurement using gas chromatography-mass spectrometry (GC-MS). Our comprehensive analysis of metabolites in the intestinal tissues detected 44 metabolites after irradiation, including amino acids, carbohydrates, organic acids, and sugars. Amino acid levels in the intestinal tissue gradually rose, dependent on the radiation dose, perhaps as an indication of oxidative stress. Our findings raise the possibility that amino acid metabolism may be a potential target for the development of treatments to alleviate or mitigate the harmful effects of oxidative stress-related gastrointestinal toxicity due to radiation exposure.

Evaluation of a Small Animal Irradiation System for Animal Experiments Using EBT3 Model GAFCHROMIC™ Film.

In cancer research, small animal models, for example, mice, rats, or rabbits, facilitate the in-depth study of biological processes and the effects of radiation treatment that can lead to breakthrough discoveries. However, the physical quality of small animal irradiation systems has not been previously evaluated. In this study, we evaluate the quality of a small animal irradiation system using GAFCHROMIC™ film and a Tough Water Phantom. The profiles and percentage depth dose curves for several irradiation conditions were measured to evaluate the quality of the irradiation system. The symmetry ratios when the table was rotated were 1.1 (no filter), 1.0 (0.5 mm Al filter), 1.0 (1.0 mm Al filter), 1.1 (2 mm Al filter), and 1.0 (filter consisting of 0.5 mm Al combined with 0.1 mm Cu). The results of measuring the percentage depth dose curve showed that the relative doses were 17.5% (10 mm depth), 12.4% (20 mm depth), 9.5% (30 mm depth), and 7.4% (40 mm filter) with no filters inserted, 78.0% (10 mm depth), 61.1% (20 mm depth), 46.9% (30 mm depth), and 35.3% (40 mm depth) when a 1.0 mm Al filter was inserted, and 94.4% (10 mm depth), 81.7% (20 mm depth), 68.1% (30 mm depth), and 54.7% (40 mm depth) when a filter consisting of 1.0 mm Al combined with 0.2 mm Cu was inserted. These physical assessments seem to be necessary especially in vivo experiments because those increase reliability of data obtained from small animal irradiation systems.

Sparing of tissue by using micro-slit-beam radiation therapy reduces neurotoxicity compared with broad-beam radiation therapy.

Micro-slit-beam radiation therapy (MRT) using synchrotron-generated X-ray beams allows for extremely high-dose irradiation. However, the toxicity of MRT in central nervous system (CNS) use is still unknown. To gather baseline toxicological data, we evaluated mortality in normal mice following CNS-targeted MRT. Male C57BL/6 J mice were head-fixed in a stereotaxic frame. Synchrotron X-ray-beam radiation was provided by the SPring-8 BL28B2 beam-line. For MRT, radiation was delivered to groups of mice in a 10 × 12 mm unidirectional array consisting of 25-µm-wide beams spaced 100, 200 or 300 µm apart; another group of mice received the equivalent broad-beam radiation therapy (BRT) for comparison. Peak and valley dose rates of the MRT were 120 and 0.7 Gy/s, respectively. Delivered doses were 96-960 Gy for MRT, and 24-120 Gy for BRT. Mortality was monitored for 90 days post-irradiation. Brain tissue was stained using hematoxylin and eosin to evaluate neural structure. Demyelination was evaluated by Klüver-Barrera staining. The LD50 and LD100 when using MRT were 600 Gy and 720 Gy, respectively, and when using BRT they were 80 Gy and 96 Gy, respectively. In MRT, mortality decreased as the center-to-center beam spacing increased from 100 µm to 300 µm. Cortical architecture was well preserved in MRT, whereas BRT induced various degrees of cerebral hemorrhage and demyelination. MRT was able to deliver extremely high doses of radiation, while still minimizing neuronal death. The valley doses, influenced by beam spacing and irradiated dose, could represent important survival factors for MRT.