title: Effect of ionizing radiation on cellular procoagulability and co-ordinated gene alterations.
abstract: OBJECTIVE
  Ionizing radiation (IR) is associated with thrombotic vascular occlusion predicting a poor clinical outcome. Our study examined whether IR induced tissue factor (TF) expression and procoagulability. We further investigated coordinated gene alterations associated with TF upregulation in the myelomonocytic leukemia THP-1 cells.
  
  
  METHODS
  TF expression was determined by quantitative Reverse Transcriptase (TaqMan) PCR, TF ELISA and TF activity by a two stage chromogenic assay in the time course of days 1, 3, 7, 10, and 17 post IR. To detect IR-induced alterations in gene expression, Affymetrix HG U133 Plus 2.0 microarrays were used. RESULTS IR induced a significant increase in TF/GAPDH mRNA ratios and cellular TF protein on days 3 and 7 post IR (20 Gy [p>or=0.01] and 40 Gy [p <or=0.01 vs. control]), suggesting a late and persistent induction of TF. An increase in cellular TF activity was already found 1 day post IR (20 Gy and 40 Gy [p>or=0.001] vs. control respectively), suggesting IR immediately alters the cellular thrombogenicity. TF upregulation post IR was confirmed in PBMNCs. Gene expression profiling showed IR increased the expression of inflammatory and apoptosis-related pathways known to be involved in the regulation of TF expression.
  
  
  CONCLUSIONS
  TF upregulation together with inflammation and apoptosis may increase the thrombogenicity of tissues. The demonstrated upregulation of TF might play a pivotal role in radiation associated thrombosis.
authors.affiliation: Department of Cardiology and Pneumology,Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany ursula.rauch@charite.de.
authors.forename: Petra
authors.initials: P
authors.lastname: Goldin-Lang
authors.forename: Klaus
authors.initials: K
authors.lastname: Pels
authors.forename: Quoc-Viet
authors.initials: QV
authors.lastname: Tran
authors.forename: Bjoern
authors.initials: B
authors.lastname: Szotowski
authors.forename: Frank
authors.initials: F
authors.lastname: Wittchen
authors.forename: Silvio
authors.initials: S
authors.lastname: Antoniak
authors.forename: Tobias
authors.initials: T
authors.lastname: Willich
authors.forename: Henning
authors.initials: H
authors.lastname: Witt
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Dido
authors.initials: D
authors.lastname: Lenze
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poller
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauch
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001779:Blood Coagulation Factors / Q000096:biosynthesis* / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000378:metabolism / Q000528:radiation effects; D004797:Enzyme-Linked Immunosorbent Assay; D015951:Factor Xa / Q000096:biosynthesis; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000528:radiation effects*; D006801:Humans; D007249:Inflammation; D015479:Leukemia, Myelomonocytic, Acute / Q000097:blood / Q000150:complications / Q000473:pathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010315:Particle Accelerators; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D011839:Radiation, Ionizing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013450:Sulfones / Q000494:pharmacology; D019851:Thrombophilia / Q000209:etiology*; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D001779:Blood Coagulation Factors; D016328:NF-kappa B; D009363:Neoplasm Proteins; D009570:Nitriles; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013450:Sulfones; C045072:macrophage procoagulant activity; D013925:Thromboplastin; D015951:Factor Xa