title: Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells.
abstract: Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid-binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation.
authors.affiliation: Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd, Seongnam-si, Gyeonggi-do, 13605, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Yim
authors.affiliation: Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd, Seongnam-si, Gyeonggi-do, 13605, Korea.
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Yun
authors.affiliation: Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd, Seongnam-si, Gyeonggi-do, 13605, Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd, Seongnam-si, Gyeonggi-do, 13605, Korea.
authors.forename: In Kyung
authors.initials: IK
authors.lastname: Lee
authors.affiliation: Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd, Seongnam-si, Gyeonggi-do, 13605, Korea.
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Nam
authors.affiliation: Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd, Seongnam-si, Gyeonggi-do, 13605, Korea.
authors.forename: Cha Soon
authors.initials: CS
authors.lastname: Kim
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D040081:Protein Array Analysis; D040901:Proteomics; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D010750:Phosphoproteins
keywords: MRC-5 cells, NHDF cells; explorer phospho antibody microarray; low-dose γ-radiation; phospho-BTK (Tyr550); phospho-Gab2 (Tyr643)