1. Changes in transcriptome after in vivo exposure to ionising radiation reveal a highly specialised liver response
- Author
-
Cyrille Petat, Sebastien Bosse, Geneviève Piétu, Diana Tronik-Le Roux, Laurie Sainz, Alexandre Pawlik, Dominique Thierry, Paul Delmar, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Ecole Centrale Paris, Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon-Université d'Évry-Val-d'Essonne (UEVE), Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
- Subjects
MESH: Gene Expression Profiling ,MESH: MyoD Protein / genetics ,Apoptosis ,Radiation Tolerance ,Transcriptome ,Mice ,0302 clinical medicine ,Radiation, Ionizing ,MESH: bcl-2-Associated X Protein / genetics ,MESH: Animals ,Oligonucleotide Array Sequence Analysis ,bcl-2-Associated X Protein ,0303 health sciences ,Radiological and Ultrasound Technology ,Kinase ,tissue response ,MESH: Tumor Necrosis Factor-alpha / genetics ,030220 oncology & carcinogenesis ,MESH: Liver / metabolism ,MESH: Radiation Tolerance ,MESH: Tumor Suppressor Protein p53 / physiology ,Cyclin-Dependent Kinase Inhibitor p21 ,Biology ,MESH: Radiation, Ionizing ,liver ,Radiosensitivity ,03 medical and health sciences ,Downregulation and upregulation ,In vivo ,MESH: Mice, Inbred C57BL ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Animals ,Radiology, Nuclear Medicine and imaging ,MESH: Cyclin-Dependent Kinase Inhibitor p21 / genetics ,Gene ,MESH: Mice ,MyoD Protein ,030304 developmental biology ,Tumor Necrosis Factor-alpha ,Gene Expression Profiling ,MESH: Apoptosis ,RNA ,Molecular biology ,Mice, Inbred C57BL ,Gene expression profiling ,MESH: Oligonucleotide Array Sequence Analysis ,Gene chip analysis ,Tumor Suppressor Protein p53 ,cDNA microarrays ,MESH: Liver / radiation effects - Abstract
International audience; Purpose: To identify transcriptional gene-networks involved in the early in vivo response of liver cells to radiation exposure and improve our understanding of the molecular processes responsible for tissue radiosensitivity.Materials and methods: Transcriptome variations of liver RNA samples were measured 3 hours post-irradiation using microarray technology. The results were confirmed and extended using real-time polymerase-chain-reaction (RT-PCR).Results: We identified quantitative changes in the expression of 126 genes, most of which were observed for the first time. We show that some modifications, such as the upregulation of the cyclin-dependent kinase inhibitor 1A (Cdkn1A) gene, persisted for at least two months after the initial exposure. Other genes regulated by the transformation-related protein 53 (Trp53/p53) such as Bcl2-associated X protein (Bax) or etoposide-induced-2.4 (Ei24/PIG8) were not upregulated. Grouping differentially expressed genes into functional categories revealed that the primary response of liver cells to radiation exposure was the enhancement of oxidoreductase activity and inhibition of cell proliferation, involving cell cycle progression and apoptosis-related genes.Conclusions: The data provides evidence of gene expression modifications associated with the hepatic response to radiation exposure. One of the main differences observed with radiation-sensitive tissues such as the spleen was cell proliferation. The comparison of our data with transcriptome modifications in different biological models enabled the identification of networks of genes that might be co-regulated. Overall, our expression data revealed genes and cellular pathways that might help to improve our understanding of the molecular basis underlying tissue radiosensitivity and to identify possible targets for novel therapeutic strategies.
- Published
- 2009
- Full Text
- View/download PDF