Changes in transcriptome after in vivo exposure to ionising radiation reveal a highly specialised liver response.
OBJECTIVE
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.


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.
Pawlik
Alexandre
A
Commissariat a l'Energie Atomique (CEA), Evry, France.
Delmar
Paul
P
Bosse
Sebastien
S
Sainz
Laurie
L
Petat
Cyrille
C
Pietu
Genevieve
G
Thierry
Dominique
D
Tronik-Le Roux
Diana
D
D000818:Animals; D017209:Apoptosis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D020869:Gene Expression Profiling; D008099:Liver / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D017570:MyoD Protein / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000235:genetics
C494827:Bax protein, mouse; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein