Schweikl H, Schmalz G
Department of Operative Dentistry and Periodontology, University of Regensburg, D-93042, Regensburg, Germany.
Mutat Res. 1999 Jan 2;438(1):71-8. doi: 10.1016/s1383-5718(98)00164-8.
Acrylate esters are applied in industrial and consumer products often associated with polymers and resins. The difunctional methacrylate, triethylene glycol dimethacrylate (TEGDMA), is also frequently included in dental composite materials. Recently, mutagenicity testing of the compound revealed the induction of gene mutations at the hprt locus in V79 cell [H. Schweikl, G. Schmalz, K. Rackebrandt, The mutagenic activity of unpolymerized resin monomers in Salmonella typhimurium and V79 cells, Mutat. Res. 415 (1998) 119-130]. In the present study, TEGDMA caused a dose dependent increase of the number of micronuclei in V79 cells. Furthermore, the mutation spectra induced in exon sequences of the hprt gene in HPRT-deficient V79 cell clones were analyzed by the polymerase chain reaction (PCR). No DNA sequence deletions were observed in spontaneously occurring HPRT-deficient cell clones at the molecular level after PCR analysis, indicating that all spontaneous mutations were caused by point mutations. However, TEGDMA treated V79 cell cultures exhibited different mutation spectra. Only one cell clone among a total of 25 contained all exon sequences of the hprt gene. Large DNA sequences were deleted in 24 cell clones. Partial gene deletions occurred in four clones from exon 5 through 9, and exon 1 was not amplified in one cell clone. Exon sequences of the hprt gene were totally deleted in 19 HPRT-deficient clones. The induction of mostly large deletions in the genome of mammalian cells, like the mutation spectra induced by TEGDMA in V79 cells here, is probably typical for crosslinking agents, including anticancer drugs. Identical types of mutations including chromosomal aberrations and the formation of micronuclei in vitro were observed for acrylates and methacrylates tested so far in various mutation assays. Therefore, we conclude by analogy that the induction of large DNA sequence deletions as shown here with the reactive dimethacrylate, triethylene glycol dimethacrylate, is probably common for acrylates and methacrylates.
丙烯酸酯类常用于工业和消费品中，这些产品通常与聚合物和树脂相关。双官能甲基丙烯酸酯，三乙二醇二甲基丙烯酸酯（TEGDMA），也经常被用于牙科复合材料中。最近，该化合物的致突变性测试显示，它能在V79细胞的hprt位点诱导基因突变[H. Schweikl, G. Schmalz, K. Rackebrandt，未聚合树脂单体在鼠伤寒沙门氏菌和V79细胞中的致突变活性，《突变研究》415 (1998) 119 - 130]。在本研究中，TEGDMA导致V79细胞中的微核数量呈剂量依赖性增加。此外，通过聚合酶链反应（PCR）分析了HPRT缺陷型V79细胞克隆中hprt基因外显子序列诱导的突变谱。PCR分析后，在分子水平上未观察到自发产生的HPRT缺陷型细胞克隆中的DNA序列缺失，这表明所有自发突变都是由点突变引起的。然而，经TEGDMA处理的V79细胞培养物表现出不同的突变谱。在总共25个细胞克隆中，只有一个包含hprt基因的所有外显子序列。24个细胞克隆中出现了大的DNA序列缺失。来自外显子5至9的四个克隆中发生了部分基因缺失，并且在一个细胞克隆中外显子1未扩增。在19个HPRT缺陷型克隆中，hprt基因的外显子序列完全缺失。哺乳动物细胞基因组中大多诱导大的缺失，就像这里TEGDMA在V79细胞中诱导的突变谱一样，可能是包括抗癌药物在内的交联剂的典型特征。对于迄今为止在各种突变试验中测试的丙烯酸酯类和甲基丙烯酸酯类，观察到相同类型的突变，包括体外染色体畸变和微核的形成。因此，我们类推得出结论，如这里所示的反应性二甲基丙烯酸酯三乙二醇二甲基丙烯酸酯诱导大的DNA序列缺失，可能是丙烯酸酯类和甲基丙烯酸酯类的共同特征。
