title: Metabolomic response of human skin tissue to low dose ionizing radiation.
abstract: Understanding how human organs respond to ionizing radiation (IR) at a systems biology level and identifying biomarkers for IR exposure at low doses can help provide a scientific basis for establishing radiation protection standards. Little is known regarding the physiological responses to low dose IR at the metabolite level, which represents the end-point of biochemical processes inside cells. Using a full thickness human skin tissue model and GC-MS-based metabolomic analysis, we examined the metabolic perturbations at three time points (3, 24 and 48 h) after exposure to 3, 10 and 200 cGy of X-rays. PLS-DA score plots revealed dose- and time-dependent clustering between sham and irradiated groups. Importantly, delayed metabolic responses were observed at low dose IR. When compared with the high dose at 200 cGy, a comparable number of significantly changed metabolites were detected 48 h after exposure to low doses (3 and 10 cGy) of irradiation. Biochemical pathway analysis showed perturbations to DNA/RNA damage and repair, lipid and energy metabolisms, even at low doses of IR.
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, 902 Battelle Blvd, PO BOX 999, MSIN K8-98, Richland, WA 99352, USA.
authors.forename: Ze-Ping
authors.initials: ZP
authors.lastname: Hu
authors.forename: Young-Mo
authors.initials: YM
authors.lastname: Kim
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Sowa
authors.forename: R Joe
authors.initials: RJ
authors.lastname: Robinson
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gao
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Metz
authors.forename: William F
authors.initials: WF
authors.lastname: Morgan
authors.forename: Qibin
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D015415:Biomarkers; D002460:Cell Line; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D055432:Metabolomics; D009696:Nucleic Acids / Q000528:radiation effects*; D011829:Radiation Dosage; D011835:Radiation Protection; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*; D049490:Systems Biology
chemical_list: D015415:Biomarkers; D009696:Nucleic Acids