Universität Ulm, Institut für Humangenetik, D-89069 Ulm, Germany.
Mutagenesis. 2011 Nov;26(6):805-11. doi: 10.1093/mutage/ger050. Epub 2011 Jul 29.
Formaldehyde (FA) was tested for a potential aneugenic activity in mammalian cells. We employed tests to discriminate between aneugenic and clastogenic effects in accordance with international guidelines for genotoxicity testing. The cytokinesis-block micronucleus test (CBMNT) in combination with fluorescence in situ hybridisation (FISH) with a pan-centromeric probe was performed with cultured human lymphocytes and the human A549 lung cell line. FA induced micronuclei (MN) in binuclear cells of both cell types under standard in vitro test conditions following the OECD guideline 487. FISH analysis revealed that the vast majority of induced MN were centromere negative, thus indicating a clastogenic effect. A similar result was obtained for MN induced by γ-irradiation, whereas the typical aneugens colcemid (COL) and vincristine (VCR) predominantly induced centromere-positive MN. Furthermore, COL and VCR clearly enhanced the MN frequency in mononuclear lymphocytes in the CBMNT, whereas such an effect was not observed for γ-irradiation and FA. In experiments with the Chinese hamster V79 cell line, the aneugens COL and VCR clearly increased the frequency of tetraploid second division metaphases, whereas FA did not cause such an effect. Altogether, our results confirm the clastogenicity of FA in cultured mammalian cells but exclude a significant aneugenic activity.
甲醛（FA）在哺乳动物细胞中进行了潜在的变倍活性测试。我们按照国际遗传毒性测试指南，采用测试来区分变倍和断裂作用。采用细胞有丝分裂阻断微核试验（CBMNT），并用荧光原位杂交（FISH）与着丝粒探针相结合，对培养的人淋巴细胞和人 A549 肺细胞系进行了试验。在 OECD 指南 487 规定的标准体外测试条件下，FA 诱导了这两种细胞类型的双核细胞中的微核（MN）。FISH 分析表明，诱导的 MN 绝大多数为着丝粒阴性，因此表明存在断裂作用。γ-辐射诱导的 MN 也得到了类似的结果，而典型的变倍剂秋水仙素（COL）和长春新碱（VCR）主要诱导着丝粒阳性 MN。此外，COL 和 VCR 明显增加了 CBMNT 中单核淋巴细胞的 MN 频率，而 γ-辐射和 FA 则没有观察到这种作用。在中华仓鼠 V79 细胞系的实验中，变倍剂 COL 和 VCR 明显增加了四倍体第二次分裂中期的频率，而 FA 则没有这种作用。总之，我们的结果证实了 FA 在培养的哺乳动物细胞中的断裂作用，但排除了其显著的变倍活性。
