title: Proteomic and genomic modulations induced by &#x03B3;-irradiation of human blood lymphocytes.
abstract: OBJECTIVE
  Quantitative evaluation of early response proteins (ERPRO) and early response genes (ERG) following γ-irradiation of human lymphocytes; identification of specific proteins and genes as candidate biomarkers for the development of a novel biodosimeter.
  
  
  METHODS
  Human peripheral blood lymphocytes were exposed to clinically relevant doses (1, 2 and 4 Gy) of γ-radiation ex-vivo. Analyses of protein and gene expression modulation were conducted 2 h post-irradiation. Global modulations were monitored using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and DNA microarray analyses of the samples originating from one human donor. On the proteome level, both phosphorylated and non-phosphorylated proteins were considered. Proteins and genes of specific interest were further targeted using Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) techniques, employing samples from several human donors (n=3).
  
  
  RESULTS
  A set of ERPRO and ERG showing significant alterations 2 h post-γ-irradiation have been identified in human lymphocytes. The most radiation responsive genes and proteins indicated alterations of cellular structure (ß-actin, talin-1 [TLN1], talin-2, zyxin-2), immune and defence reactions (major histocompatibility complex binding protein-2 [MBP2], interleukin-17E and interferon-γ), cell cycle control (cyclin-dependent kinase inhibitor-1A [CDKN1A], mouse double minute-2, annexin-A6 [ANXA6], growth arrest and DNA-damage-inducible protein-α [GADD45A], proliferating cell nuclear antigen [PCNA], dual specificity phosphatase-2 and 8 [DUSP8]) as well as detoxification processes (peroxin-1) and apoptosis (B-cell lymphoma-2 binding component-3 [BBC3]).
  
  
  CONCLUSIONS
  The estimations of protein concentration modulation of TLN1 and CDKN1A, phosphorylation status of ANXA6 (dose range 0-2 Gy) and MBP2 as well as the alterations in the level of gene expressions of BBC3, DUSP8, GADD45A and PCNA appears to be of potential value for future biodosimetric applications.
authors.affiliation: Department of Safety and Radiation Protection, Research Centre Jülich, Germany. a.turtoi@ulg.ac.be
authors.forename: Andrei
authors.initials: A
authors.lastname: Turtoi
authors.forename: Rajeshwar N
authors.initials: RN
authors.lastname: Sharan
authors.forename: Alok
authors.initials: A
authors.lastname: Srivastava
authors.forename: Frank H A
authors.initials: FH
authors.lastname: Schneeweiss
mesh_terms: D000328:Adult; D015153:Blotting, Western; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000528:radiation effects*; D023281:Genomics; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism* / Q000528:radiation effects*; D008297:Male; D013058:Mass Spectrometry; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome / Q000528:radiation effects*; D040901:Proteomics; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D020543:Proteome