title: Dose-dependent metabolic alterations in human cells exposed to gamma irradiation.
abstract: 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.
authors.affiliation: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, 120-140, Republic of Korea.
authors.forename: Yong-Kook
authors.initials: YK
authors.lastname: Kwon
authors.affiliation: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, 120-140, Republic of Korea.
authors.forename: In Jin
authors.initials: IJ
authors.lastname: Ha
authors.affiliation: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, 120-140, Republic of Korea; Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764, Republic of Korea.
authors.forename: Hyun-Whee
authors.initials: HW
authors.lastname: Bae
authors.affiliation: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, 120-140, Republic of Korea; Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764, Republic of Korea.
authors.forename: Won Gyo
authors.initials: WG
authors.lastname: Jang
authors.affiliation: Division of Radiation Effect, Korea Institute of Radiological & Medical Sciences, Seoul, 139-706, Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Yun
authors.affiliation: Division of Radiation Effect, Korea Institute of Radiological & Medical Sciences, Seoul, 139-706, Korea.
authors.forename: So Ra
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Division of Radiation Effect, Korea Institute of Radiological & Medical Sciences, Seoul, 139-706, Korea.
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Division of Radiation Effect, Korea Institute of Radiological & Medical Sciences, Seoul, 139-706, Korea.
authors.forename: Chang-Mo
authors.initials: CM
authors.lastname: Kang
authors.affiliation: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, 120-140, Republic of Korea; Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764, Republic of Korea.
authors.forename: Geum-Sook
authors.initials: GS
authors.lastname: Hwang
mesh_terms: D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D020405:Dermis / Q000166:cytology; D016002:Discriminant Analysis; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D016018:Least-Squares Analysis; D013058:Mass Spectrometry / Q000379:methods; D055442:Metabolome / Q000528:radiation effects*; D055432:Metabolomics; D015999:Multivariate Analysis; D025341:Principal Component Analysis; D013997:Time Factors