2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation
2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation
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DOI：
10.1007/s11033-011-0895-y
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发表时间：
2012-02-01
影响因子：
2.8
通讯作者：
Blasiak, Janusz
中科院分区：
文献类型：
--
作者：
Szczepanska, Joanna;Poplawski, Tomasz;Blasiak, Janusz
甲基丙烯酸羟乙酯(HEMA)是一种牙科常用的甲基丙烯酸甲酯，已有报道可引起遗传毒性作用，但其作用机制尚不完全清楚。HEMA可能会被口腔中的酯酶或咀嚼过程中的机械应力降解。甲基丙烯酸(MAA)是HEMA降解的主要产物。在本工作中，我们比较了HEMA和MAA对人牙龈成纤维细胞(HGFs)的细胞毒性和遗传毒性作用。HEMA或MAA暴露6h后，HGFs的活性略有下降。HEMA和MAA均不能引起HGFDNA链断裂，但碱性彗星试验表明两种化合物均可引起HGFs DNA损伤。DNA修复酶Endo III和FPG监测DNA碱基的氧化修饰。HEMA和MAA引起的DNA损伤不是持续性的，在120min的修复孵育过程中被清除。中性彗星实验结果表明，两种化合物均可引起DNA双链断裂(DSB)，并被γ-H_2AX实验所证实。这两种化合物都能诱导细胞凋亡并扰乱细胞周期。因此，HEMA降解产物甲基丙烯酸可能参与其细胞毒性和遗传毒性作用。
HEMA (2-hydroxyethyl methacrylate), a methacrylate commonly used in dentistry, was reported to induce genotoxic effects, but their mechanism is not fully understood. HEMA may be degraded by the oral cavity esterases or through mechanical stress following the chewing process. Methacrylic acid (MAA) is the primary product of HEMA degradation. In the present work we compared cytotoxic and genotoxic effects induced by HEMA and MAA in human gingival fibroblasts (HGFs). A 6-h exposure to HEMA or MAA induced a weak decrease in the viability of HGFs. Neither HEMA nor MAA induced strand breaks in the isolated plasmid DNA, but both compounds evoked DNA damage in HGFs, as evaluated by the alkaline comet assay. Oxidative modifications to the DNA bases were monitored by the DNA repair enzymes Endo III and Fpg. DNA damage induced by HEMA and MAA was not persistent and was removed during a 120 min repair incubation. Results from the neutral comet assay indicated that both compounds induced DNA double strand breaks (DSBs) and they were confirmed by the gamma-H2AX assay. Both compounds induced apoptosis and perturbed the cell cycle. Therefore, methacrylic acid, a product of HEMA degradation, may be involved in its cytotoxic and genotoxic action.