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Effect of ionizing radiation on cellular procoagulability and co-ordinated gene alterations
Effect of ionizing radiation on cellular procoagulability and co-ordinated gene alterations
- Source :
- Haematologica. 92(8)
- Publication Year :
- 2006
-
Abstract
- Background and Objectives: 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. Design and 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≤0.01] and 40 Gy [p≤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≥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. Interpretation and 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.
- Subjects :
- Inflammation
Apoptosis
Enzyme-Linked Immunosorbent Assay
Biology
Leukemia, Myelomonocytic, Acute
Thromboplastin
Tissue factor
Downregulation and upregulation
Cell Line, Tumor
Radiation, Ionizing
Gene expression
Nitriles
medicine
Humans
Thrombophilia
RNA, Messenger
RNA, Neoplasm
Sulfones
Oligonucleotide Array Sequence Analysis
Regulation of gene expression
Gene Expression Regulation, Leukemic
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
NF-kappa B
Hematology
medicine.disease
Molecular biology
Blood Coagulation Factors
Neoplasm Proteins
Gene expression profiling
Leukemia
Immunology
Factor Xa
medicine.symptom
Particle Accelerators
Subjects
Details
- ISSN :
- 15928721
- Volume :
- 92
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Haematologica
- Accession number :
- edsair.doi.dedup.....fd011640ff141fc4747ddcffecc0433b