Stimulation of glutathione depletion, ROS production and cell cycle arrest of dental pulp cells and gingival epithelial cells by HEMA.
2-Hydroxy-ethyl methacrylate (HEMA) is the major component released from resin-modified glass ionomer cements and dental adhesives. Human tissues mainly affected by HEMA are oral epithelium and dental pulp. We treated human gingival epithelial S-G cells and pulp fibroblasts (HPF) with various concentrations of HEMA, to evaluate its effects on cell growth, cell cycle progression, intracellular glutathione (GSH) level and reactive oxygen species (ROS) production. HEMA-induced growth inhibition in HPF and S-G cells in a dose-dependent manner, which may be partially explained by induction of cell cycle perturbation. G(2)/M phase arrest was noted after exposure of HPF to 5 and 10mm of HEMA, concomitant with glutathione depletion and ROS production. S-phase arrest occurred in S-G cells when treated with 2.5 and 5mm, while at 10mm a sub-G(0)/G(1) peak was noted, indicating the potential induction of apoptosis. GSH depletion was marked in S-G cells only at concentrations of 5 and 10mm, but excessive ROS production was noted at concentration of 1mm and rose with dose increase between 1 and 5mm, then lessened at 10mm. This suggested that the increase of ROS in S-G cells was not mainly caused by GSH depletion. These results helped to define the mechanism of the cytotoxicity caused by HEMA.
Chang
Hsiao-Hua
HH
Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Guo
Ming-Kuang
MK
Kasten
Frederick H
FH
Chang
Mei-Chi
MC
Huang
Guay-Fen
GF
Wang
Yin-Lin
YL
Wang
Ruey-Song
RS
Jeng
Jiiang-Huei
JH
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003738:Dental Cements / Q000009:adverse effects; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008422:Materials Testing; D008689:Methacrylates / Q000009:adverse effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D003738:Dental Cements; D008689:Methacrylates; D017382:Reactive Oxygen Species; C005044:hydroxyethyl methacrylate; D005978:Glutathione