Differential gene expression involved in oxidative stress response caused by triethylene glycol dimethacrylate.
Triethylene glycol dimethacrylate (TEGDMA) is a comonomer that is released from dental resin-based materials into hydrophilic solvents. The compound reduces cell vitality, and causes genotoxicity in mammalian cells in vitro. Here, we used gene expression profiling, combined with pathway analysis tools, to identify the molecular events associated with TEGDMA cytotoxicity in human fibroblasts using Affymetrix HG-U133A 2.0 GeneChip arrays. Increased ROS production and a cell cycle delay caused by 3mm TEGDMA after a 6h exposure were related to a cell response at the transcriptional level. The predominant biological processes associated with the genes that were differentially expressed in untreated and treated cell cultures included oxidative stress, cellular growth, proliferation and morphology, cell death, gene expression as well as DNA replication and repair. The most significantly upregulated genes were GEM (17-fold), KLHL24, DDIT4, TGIF, DUSP5 and ATF3, which are all related to the regulation of the cell structure, stress response, and cell proliferation. TXNIP was the most downregulated transcript (five-fold), whose gene product regulates the cellular redox balance. The downregulation of NRG1, ASPM, FBXO5, and PLK2 is linked to the regulation of cell proliferation and cell structure. The underlying mechanisms of the up- and downregulation of genes seem to be activated by the production of ROS, and the related regulation of the cellular redox balance disturbed in the presence of TEGDMA appears to be of the utmost importance. The coordinated induction of genes coding for oxidative stress response and antioxidant proteins is a critical mechanism of protection against TEGDMA-induced cell damage.
Schweikl
Helmut
H
Department of Operative Dentistry and Periodontology, University of Regensburg, D-93042 Regensburg, Germany. helmut.schweikl@klinik.uni-regensburg.de <helmut.schweikl@klinik.uni-regensburg.de>
Hiller
Karl-Anton
KA
Eckhardt
Alexander
A
Bolay
Carola
C
Spagnuolo
Gianrico
G
Stempfl
Thomas
T
Schmalz
Gottfried
G
D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003188:Composite Resins / Q000494:pharmacology; D003764:Dental Materials / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011109:Polymethacrylic Acids / Q000494:pharmacology*
D003188:Composite Resins; D003764:Dental Materials; D011109:Polymethacrylic Acids; C020946:triethylene glycol dimethacrylate; D011092:Polyethylene Glycols