Speit Günter, Schmid Oliver
Universität Ulm, Abteilung Humangenetik, D-89070 Ulm, Germany.
Mutat Res. 2006 Sep;613(1):1-9. doi: 10.1016/j.mrrev.2006.02.002. Epub 2006 Apr 25.
Formaldehyde (FA) is genotoxic in vitro in cultured mammalian cells. When FA reaches the nuclear DNA, it forms DNA-protein cross-links (DPX). Incomplete repair of DPX can lead to the formation of mutations, in particular chromosome mutations and micronuclei (MN) in proliferating cells. Due to its high reactivity, FA leads primarily to local genotoxic effects at the site of contact. In humans, local genotoxic effects of FA have been studied with the micronucleus test (MNT) in exfoliated nasal and buccal mucosa cells. This approach is considered to be highly relevant because these tissues are the actual targets of FA, and MN are a sensitive indicator for the mutagenic action of FA. The published studies suggest that inhalation of FA leads to increased MN frequencies in nasal and/or buccal mucosa cells. However, a critical review of the data reveals that the effects are not consistent, and the studies should be interpreted with caution. One problem is the lack of standardization of the MNT with exfoliated cells and the high assay variability. Another problem concerns the quality of published studies indicating local genotoxic effects of FA in humans. Incomplete information on study design, exposure, and confounding factors frequently limit the interpretation of these studies. On the basis of the available data, it is not yet possible to assess the local genotoxicity of FA in humans and to draw meaningful conclusions with regard to a dose-effect relationship for risk estimation.
甲醛（FA）在体外培养的哺乳动物细胞中具有遗传毒性。当FA到达核DNA时，它会形成DNA-蛋白质交联（DPX）。DPX修复不完全会导致突变的形成，特别是增殖细胞中的染色体突变和微核（MN）。由于其高反应性，FA主要在接触部位产生局部遗传毒性作用。在人类中，已通过对脱落的鼻黏膜和颊黏膜细胞进行微核试验（MNT）来研究FA的局部遗传毒性作用。这种方法被认为高度相关，因为这些组织是FA的实际作用靶点，而MN是FA诱变作用的敏感指标。已发表的研究表明，吸入FA会导致鼻黏膜和/或颊黏膜细胞中的MN频率增加。然而，对这些数据的严格审查发现，结果并不一致，对这些研究的解读应谨慎。一个问题是对脱落细胞进行MNT缺乏标准化，且检测变异性高。另一个问题涉及已发表的表明FA对人类具有局部遗传毒性作用的研究质量。关于研究设计、暴露情况和混杂因素的信息不完整常常限制了对这些研究的解读。根据现有数据，尚无法评估FA对人类的局部遗传毒性，也无法就风险评估的剂量-效应关系得出有意义的结论。
