Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells

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 highdose 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. © the author 2017. published by oxford university press on behalf of the japan radiation research society and japanese society for radiation oncology.