Investigation of relative metabolic changes in the organs and plasma of rats exposed to X-ray radiation using HR-MAS (1)H NMR and solution (1)H NMR.

Excess exposure to ionizing radiation generates reactive oxygen species and increases the cellular inflammatory response by modifying various metabolic pathways. However, an investigation of metabolic perturbations and organ-specific responses based on the amount of radiation during the acute phase has not been conducted. In this study, high-resolution magic-angle-spinning (HR-MAS) NMR and solution NMR-based metabolic profiling were used to investigate dose-dependent metabolic changes in multiple organs and tissues--including the jejunum, spleen, liver, and plasma--of rats exposed to X-ray radiation. The organs, tissues, and blood samples were obtained 24, 48, and 72 h after exposure to low-dose (2 Gy) and high-dose (6 Gy) X-ray radiation and subjected to metabolite profiling and multivariate analyses. The results showed the time course of the metabolic responses, and many significant changes were detected in the high-dose compared with the low-dose group. Metabolites with antioxidant properties showed acute responses in the jejunum and spleen after radiation exposure. The levels of metabolites related to lipid and protein metabolism were decreased in the jejunum. In addition, amino acid levels increased consistently at all post-irradiation time points as a consequence of activated protein breakdown. Consistent with these changes, plasma levels of tricarboxylic acid cycle intermediate metabolites decreased. The liver did not appear to undergo remarkable metabolic changes after radiation exposure. These results may provide insight into the major metabolic perturbations and mechanisms of the biological systems in response to pathophysiological damage caused by X-ray radiation.

Dose-dependent metabolic alterations in human cells exposed to gamma irradiation.

Radiation exposure is a threat to public health because it causes many diseases, such as cancers and birth defects, due to genetic modification of cells. Compared with the past, a greater number of people are more frequently exposed to higher levels of radioactivity today, not least due to the increased use of diagnostic and therapeutic radiation-emitting devices. In this study, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS)-based metabolic profiling was used to investigate radiation- induced metabolic changes in human fibroblasts. After exposure to 1 and 5 Gy of γ-radiation, the irradiated fibroblasts were harvested at 24, 48, and 72 h and subjected to global metabolite profiling analysis. Mass spectral peaks of cell extracts were analyzed by pattern recognition using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The results showed that the cells irradiated with 1 Gy returned to control levels at 72 h post radiation, whereas cells irradiated with 5 Gy were quite unlike the controls; therefore, cells irradiated with 1 Gy had recovered, whereas those irradiated with 5 Gy had not. Lipid and amino acid levels increased after the higher-level radiation, indicating degradation of membranes and proteins. These results suggest that MS-based metabolite profiling of γ-radiation-exposed human cells provides insight into the global metabolic alterations in these cells.