Ginzkey Christian, Zinnitsch Sabrina, Steussloff Gudrun, Koehler Christian, Hackenberg Stephan, Hagen Rudolf, Kleinsasser Norbert H, Froelich Katrin
Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany.
Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany.
Dent Mater. 2015 Aug;31(8):865-76. doi: 10.1016/j.dental.2015.04.009. Epub 2015 May 27.
Residual unbound resin monomers of 2-hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA) are known to diffuse in the saliva and through dentin and pulp into the blood and may affect cellular integrity. The current study was performed to investigate the genotoxic potential of both monomers in distinctly lower concentrations than known to cause cytotoxic damage.
Lymphocytes from 10 healthy volunteers were treated with HEMA (10μM-1mM) and TEGDMA (1μM-100μM) for 24h. Cell viability, apoptosis and influence on cell cycle kinetics were assessed by flowcytometry. DNA damage was determined by the alkali version of the comet assay in combination with the FPG protein and by the cytokinesis-block micronucleus (CBMN) test. Additionally, the chromosome aberration (CA) test and sister chromatid exchange (SCE) test were performed.
A slight decrease in cell viability was detected only at the highest concentration of TEGDMA. Genotoxic effects were measurable in the comet assay at 1mM of HEMA and 100μM of TEGDMA, with and without FPG protein, but not in the CBMN test or the cell cycle analysis. Contrary to these findings, a significant dose-dependent increase in the frequency of CAs and SCEs could be demonstrated in all tested concentrations.
This is the first time clastogenic responses to HEMA and TEGDMA have been detected in concentrations distinctly lower than those reported for causing cytotoxic or even genotoxic effects. These findings underline the importance of using test batteries with different genotoxicological endpoints to describe the multiple effects of both resin monomers.
已知甲基丙烯酸2-羟乙酯(HEMA)和二甲基丙烯酸三甘醇酯(TEGDMA)的残留未结合树脂单体可扩散至唾液中,并通过牙本质和牙髓进入血液,可能影响细胞完整性。本研究旨在探究这两种单体在明显低于已知会导致细胞毒性损伤浓度时的遗传毒性潜力。
将来自10名健康志愿者的淋巴细胞用HEMA(10μM - 1mM)和TEGDMA(1μM - 100μM)处理24小时。通过流式细胞术评估细胞活力、凋亡及对细胞周期动力学的影响。DNA损伤通过彗星试验的碱性版本结合FPG蛋白以及胞质分裂阻滞微核(CBMN)试验来确定。此外,还进行了染色体畸变(CA)试验和姐妹染色单体交换(SCE)试验。
仅在TEGDMA的最高浓度下检测到细胞活力略有下降。在彗星试验中,无论有无FPG蛋白,在1mM的HEMA和100μM的TEGDMA浓度下均可检测到遗传毒性效应,但在CBMN试验或细胞周期分析中未检测到。与这些结果相反,在所有测试浓度下均可证明CA和SCE频率有显著的剂量依赖性增加。
这是首次在明显低于报道的导致细胞毒性甚至遗传毒性效应的浓度下检测到对HEMA和TEGDMA的致断裂反应。这些发现强调了使用具有不同遗传毒理学终点的测试组合来描述这两种树脂单体多种效应的重要性。