The effect of triethylene glycol dimethacrylate on p53-dependent G2 arrest in human gingival fibroblasts.
Dental resin composites have been reported to exert adverse effects on cells of the oral cavity. In this study, we demonstrate that a non-cytotoxic concentration of the resin co-monomer triethylene glycol dimethacrylate (TEGDMA) results in the reduction of the proliferation rate of human gingival fibroblasts (HGFs), by delaying them at the G2 phase of the cell cycle, and in the sustained production of reactive oxygen species. These phenomena are accompanied by an early transient de-phosphorylation of ERK1/2 and JNKs and a late activation of the p53-p21(WAF1)-pRb molecular pathway. By using siRNA-mediated knocking down of the human p53 gene, we present evidence that the onco-suppressive protein p53 controls the TEGDMA-activated G2 checkpoint in HGFs and prevents their entry into mitosis, possibly in order to protect them from the detrimental genotoxic effects of the compound.
Mavrogonatou
Eleni
E
Laboratory of Cell Proliferation and Ageing, Institute of Biology, National Centre for Scientific Research Demokritos, 153 10 Athens, Greece.
Eliades
Theodore
T
Eliades
George
G
Kletsas
Dimitris
D
D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D016195:G2 Phase / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011109:Polymethacrylic Acids / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D018797:Cell Cycle Proteins; D011109:Polymethacrylic Acids; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C020946:triethylene glycol dimethacrylate; D011092:Polyethylene Glycols; D020928:Mitogen-Activated Protein Kinases