Eckhardt Alexander, Gerstmayr Nicol, Hiller Karl-Anton, Bolay Carola, Waha Claudia, Spagnuolo Gianrico, Camargo Carlos, Schmalz Gottfried, Schweikl Helmut
Department of Operative Dentistry and Periodontology, University of Regensburg, Regensburg, Germany.
Biomaterials. 2009 Apr;30(11):2006-14. doi: 10.1016/j.biomaterials.2008.12.045. Epub 2009 Jan 12.
The development of strategies for the protection of oral tissues against the adverse effects of resin monomers is primarily based on the elucidation of underlying molecular mechanisms. The generation of reactive oxygen species beyond the capacity of a balanced redox regulation in cells is probably a cause of cell damage. This study was designed to investigate oxidative DNA damage, the activation of ATM, a reporter of DNA damage, and redox-sensitive signal transduction through mitogen-activated protein kinases (MAPKs) by the monomer triethylene glycol dimethacrylate (TEGDMA). TEGDMA concentrations as high as 3-5 mM decreased THP-1 cell viability after a 24h and 48h exposure, and levels of 8-oxoguanine (8-oxoG) increased about 3- to 5-fold. The cells were partially protected from toxicity in the presence of N-acetylcysteine (NAC). TEGDMA also induced a delay in the cell cycle. The number of THP-1 cells increased about 2-fold in G1 phase and 5-fold in G2 phase in cultures treated with 3-5 mM TEGDMA. ATM was activated in THP-1 cells by TEGDMA. Likewise, the amounts of phospho-p38 were increased about 3-fold by 3 mM TEGDMA compared to untreated controls after a 24h and 48h exposure period, and phospho-ERK1/2 was induced in a very similar way. The activation of both MAPKs was inhibited by NAC. Our findings suggest that the activation of various signal transduction pathways is related to oxidative stress caused by a resin monomer. Signaling through ATM indicates oxidative DNA damage and the activation of MAPK pathways indicates oxidative stress-induced regulation of cell survival and apoptosis.
开发保护口腔组织免受树脂单体不良影响的策略主要基于对潜在分子机制的阐明。细胞内活性氧的产生超出了平衡氧化还原调节的能力，这可能是细胞损伤的一个原因。本研究旨在调查单体三乙二醇二甲基丙烯酸酯（TEGDMA）对氧化性DNA损伤、DNA损伤报告分子ATM的激活以及通过丝裂原活化蛋白激酶（MAPK）的氧化还原敏感信号转导的影响。在暴露24小时和48小时后，高达3-5 mM的TEGDMA浓度会降低THP-1细胞活力，并且8-氧代鸟嘌呤（8-oxoG）水平增加约3至5倍。在N-乙酰半胱氨酸（NAC）存在下，细胞的毒性得到部分保护。TEGDMA还诱导细胞周期延迟。在用3-5 mM TEGDMA处理的培养物中，THP-1细胞在G1期增加约2倍，在G2期增加约5倍。TEGDMA在THP-1细胞中激活了ATM。同样，在暴露24小时和48小时后，与未处理的对照相比，3 mM TEGDMA使磷酸化p38的量增加约3倍，磷酸化ERK1/2也以非常相似的方式被诱导。NAC抑制了两种MAPK的激活。我们的研究结果表明，各种信号转导途径的激活与树脂单体引起的氧化应激有关。通过ATM的信号传导表明氧化性DNA损伤，而MAPK途径的激活表明氧化应激诱导的细胞存活和凋亡调节。
