Effect of irradiation on cell transcriptome and proteome of rat submandibular salivary glands.
Salivary glands (SGs) are irreversibly damaged by irradiation (IR) treatment in head and neck cancer patients. Here, we used an animal irradiation model to investigate and define the molecular mechanisms affecting SGs following IR, focusing on saliva proteome and global transcription profile of submandibular salivary gland (SSG) tissue.We show that saliva secretion was gradually reduced to 50% of its initial level 12 weeks post-IR. Saliva protein composition was further examined by proteomic analysis following mass spectrometry (MS) analysis that revealed proteins with reduced expression originating from SSGs and proteins with increased expression derived from the serum, both indicating salivary tissue damage. To examine alterations in mRNA expression levels microarray analysis was performed. We found significant alterations in 95 genes, including cell-cycle arrest genes, SG functional genes and a DNA repair gene.Tissue damage was seen by confocal immunofluorescence of α-amylase and c-Kit that showed an increase and decrease, respectively, in protein expression. This was coherent with real-time PCR results.This data indicates that IR damages the SSG cells' ability to produce and secrete saliva and proteins, and maintain the physiological barrier between serum and saliva. The damage does not heal due to cell-cycle arrest, which prevents tissue regeneration. Taken together, our results reveal a new insight into IR pathobiology.
Faculty of Dental Medicine, Institute of Dental Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Raluca
R
Stiubea-Cohen
Ran
R
David
Yoav
Y
Neumann
Guy
G
Krief
Omer
O
Deutsch
Batia
B
Zacks
Doron J
DJ
Aframian
Aaron
A
Palmon
D000818:Animals; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects; D020543:Proteome / Q000528:radiation effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012463:Saliva / Q000378:metabolism; D013363:Submandibular Gland / Q000378:metabolism* / Q000528:radiation effects*; D013997:Time Factors; D059467:Transcriptome / Q000528:radiation effects*
D020543:Proteome