title: Dynamic changes in the proteome of human peripheral blood mononuclear cells with low dose ionizing radiation.
abstract: Humans are continually exposed to ionizing radiation from natural as well as anthropogenic sources. Though biological effects of high dose radiation exposures have been well accepted, studies on low-to-moderate dose exposures (in the range of 50-500 mGy) have been strongly debated even as researchers continue to search for elusive 'radiation signatures' in humans. Proteins are considered as dynamic functional players that drive cellular responses. However, there is little proteomic information available in context of human exposure to ionizing radiation. In this study, we determined differential expressed proteins in G0 peripheral blood mononuclear cells (PBMCs) from healthy individuals 1h and 4h after 'ex vivo' exposure with two radiation doses (300 mGy and 1 Gy). Twenty-three proteins were found to be significantly altered in irradiated cells when compared to sham irradiated cells with fold change ± 1.5-fold (p ≤ 0.05), with only three proteins showing ≥ 2.5-fold change, either with dose or with time. Mass spectrometry analyses identified redox sensor protein, chloride intracellular channel protein 1 (CLIC-1), the antioxidant protein, peroxiredoxin-6 and the pro-survival molecular chaperone 78 KDa glucose regulated protein (GRP78) among the 23 modulated proteins. The mean coefficient of variation (CV) for the twenty-three radiation responsive protein spots was found to be 33.7% for 300 mGy and 48.3% for 1 Gy. We thus, conclude that the radiation proteomic response of G0 human PBMCs, which are in the resting stage of the cell cycle, involves moderate upregulation of protective mechanisms, with low inter-individual variability. This study will help further our understanding of cellular effects of low dose acute radiation in humans and contribute toward differential biomarker discovery.
authors.affiliation: Radiation Signaling Group, Radiation Signaling & Cancer Biology Section, Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.
authors.forename: S
authors.initials: S
authors.lastname: Nishad
authors.affiliation: Radiation Signaling Group, Radiation Signaling & Cancer Biology Section, Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India. Electronic address: anugh@barc.gov.in.
authors.forename: Anu
authors.initials: A
authors.lastname: Ghosh
mesh_terms: D000328:Adult; D002470:Cell Survival / Q000528:radiation effects; D018118:Chloride Channels / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000378:metabolism; D010084:Oxidation-Reduction; D054465:Peroxiredoxin VI / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D011839:Radiation, Ionizing; D015854:Up-Regulation
chemical_list: C501966:CLIC1 protein, human; D018118:Chloride Channels; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D020543:Proteome; D054465:Peroxiredoxin VI
keywords: Acute low dose radiation; Human peripheral blood mononuclear cells; MALDI-TOF MS; Two dimensional gel based proteomics (2-DE)