title: Identification of low-dose responsive metabolites in X-irradiated human B lymphoblastoid cells and fibroblasts.
abstract: Ionizing radiation (IR) induces cellular stress responses, such as signal transduction, gene expression, protein modification, and metabolite change that affect cellular behavior. We analyzed X-irradiated human Epstein-Barr virus-transformed B lymphoblastoid cells and normal fibroblasts to search for metabolites that would be suitable IR-responsive markers by Liquid Chromotography-Mass spectrometry (LC-MS). Mass spectra, as analyzed with principal component analysis, showed that the proportion of peaks with IR-induced change was relatively small compared with the influence of culture time. Dozens of peaks that had either been upregulated or downregulated by IR were extracted as candidate IR markers. The IR-changed peaks were identified by comparing mock-treated groups to 100 mGy-irradiated groups that had recovered after 10 h, and the results indicated that the metabolites involved in nucleoside synthesis increased and that some acylcarnitine levels decreased in B lymphoblastoids. Some peaks changed by as much as 20 mGy, indicating the presence of an IR-sensitive signal transduction/metabolism control mechanism in these cells. On the other hand, we could not find common IR-changed peaks in fibroblasts of different origin. These data suggest that cell phenotype-specific pathways exist, even in low-dose responses, and could determine cell behavior.
authors.affiliation: Department of Radiation Life Sciences, Fukushima Medical University, 1 Hikarigaoka, Fukushima-shi, Fukushima 960-1295, Japan tsuyama@fmu.ac.jp.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Tsuyama
authors.affiliation: Quantitative Biology Center (QBiC), RIKEN, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Mizuno
authors.affiliation: Department of Radiation Life Sciences, Fukushima Medical University, 1 Hikarigaoka, Fukushima-shi, Fukushima 960-1295, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Katafuchi
authors.affiliation: Department of Radiation Life Sciences, Fukushima Medical University, 1 Hikarigaoka, Fukushima-shi, Fukushima 960-1295, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Department of Radiation Life Sciences, Fukushima Medical University, 1 Hikarigaoka, Fukushima-shi, Fukushima 960-1295, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kurosu
authors.affiliation: Department of Radiation Life Sciences, Fukushima Medical University, 1 Hikarigaoka, Fukushima-shi, Fukushima 960-1295, Japan Institute of Radiation Emergency Medicine, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Radiation Life Sciences, Fukushima Medical University, 1 Hikarigaoka, Fukushima-shi, Fukushima 960-1295, Japan Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kamiya
authors.affiliation: Department of Radiation Life Sciences, Fukushima Medical University, 1 Hikarigaoka, Fukushima-shi, Fukushima 960-1295, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sakai
mesh_terms: D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism* / Q000528:radiation effects*; D006801:Humans; D009696:Nucleic Acids / Q000378:metabolism*; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism* / Q000528:radiation effects*; D011829:Radiation Dosage; D015398:Signal Transduction / Q000502:physiology* / Q000528:radiation effects; D014965:X-Rays
chemical_list: D009696:Nucleic Acids
keywords: B lymphoblastoid cell; LC–MS; X-irradiation; fibroblast; low-dose radiation; metabolomics