1H NMR-based Metabolomics to Study Effects of Ionizing Radiation in Human Lymphocytes
Date Issued
2012
Date
2012
Author(s)
Liu, Heng-Chun
Abstract
Although epidemiological studies have demonstrated adverse human health effects with a greater risk for cancer development when subjects are exposed to ionizing radiation, the mechanisms of biological impacts are still unclear despite the increasing use of diagnostic radiology in medicine. In recent years, several functional genomic approaches have been developed and applied to examine molecular events in biological systems exposed to ionizing radiation. Little metabolomic studies were conducted on the metabolic effects of ionizing radiation. Therefore, we intend to use metabolomic approach to understand the molecular events in a more functional measurement. Human lymphoblastic cell lines: TK6 (wild-type p53) and WTK1 (mutant p53) were used to examine metabolic effects of ionizing radiation. Time-course and dose-response experiments were conducted in cells treated with gamma-ray （iso-survival dose, D0 (TK6: 0.8 Gy; WTK1: 1.5 Gy） or 10 Gy) for 3 or 24 hours. Hydrophilic and hydrophobic metabolites were extracted and analyzed by 1H and J-resolved NMR followed by principal component analysis and metabolite identification. Based on our results, both hydrophilic and hydrophobic metabolome are shown different radiation effects between TK6 and WTK1 cells. The γ-ray radiation effects on hydrophilic metabolome at 24 hours are greater than at 3 hours both in different cell types and doses. The dose effect of ionizing radiation on the WTK1 may be related to intracellular oxidative stress. In summary, after γ-ray exposure, the hydrophilic metabolome changing in cells may caused by oxidative stress, cell membrane damage, apoptosis and DNA damage. The various p53 status also results in differences in taurine, alanine, creatine and glutathione between TK6 and WTK1 cells.
Subjects
nuclear magnetic resonance (NMR)
human lymphocytes
ionizing radiation
metabolomics
SDGs
Type
thesis
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