The unique physicochemical properties of multi-walled carbon nanotubes (MWCNT) have led to many industrial applications. Due to their low density and small size, MWCNT are easily aerosolized in the workplace making respiratory exposures likely in workers. The International Agency for Research on Cancer designated the pristine Mitsui-7 MWCNT (MWCNT-7) as a Group 2B carcinogen, but there was insufficient data to classify all other MWCNT. Previously, MWCNT exposed to high temperature (MWCNT-HT) or synthesized with nitrogen (MWCNT-ND) have been found to elicit attenuated toxicity; however, their genotoxic and carcinogenic potential are not known. Our aim was to measure the genotoxicity of MWCNT-7 compared to these two physicochemically-altered MWCNTs in human lung epithelial cells (BEAS-2B & SAEC). Dose-dependent partitioning of individual nanotubes in the cell nuclei was observed for each MWCNT material and was greatest for MWCNT-7. Exposure to each MWCNT led to significantly increased mitotic aberrations with multi- and monopolar spindle morphologies and fragmented centrosomes. Quantitative analysis of the spindle pole demonstrated significantly increased centrosome fragmentation from 0.024–2.4 μg/mL of each MWCNT. Significant aneuploidy was measured in a dose-response from each MWCNT-7, HT, and ND; the highest dose of 24 μg/mL produced 67, 61, and 55%, respectively. Chromosome analysis demonstrated significantly increased centromere fragmentation and translocations from each MWCNT at each dose. Following 24 h of exposure to MWCNT-7, ND and/or HT in BEAS-2B a significant arrest in the G1/S phase in the cell cycle occurred, whereas the MWCNT-ND also induced a G2 arrest. Primary SAEC exposed for 24 h to each MWCNT elicited a significantly greater arrest in the G1 and G2 phases. However, SAEC arrested in the G1/S phase after 72 h of exposure. Lastly, a significant increase in clonal growth was observed one month after exposure to 0.024 μg/mL MWCNT-HT & ND. Although MWCNT-HT & ND cause a lower incidence of genotoxicity, all three MWCNTs cause the same type of mitotic and chromosomal disruptions. Chromosomal fragmentation and translocations have not been observed with other nanomaterials. Because in vitro genotoxicity is correlated with in vivo genotoxic response, these studies in primary human lung cells may predict the genotoxic potency in exposed human populations.

中文翻译：

---

经热处理和氮掺杂的Mitsui-7多壁碳纳米管在人肺上皮细胞中引起遗传毒性。

多壁碳纳米管（MWCNT）的独特理化性质已导致许多工业应用。由于低密度和小尺寸，MWCNT容易在工作场所雾化，使工人容易接触呼吸。国际癌症研究机构将原始的Mitsui-7 MWCNT（MWCNT-7）指定为2B组致癌物，但没有足够的数据来分类所有其他MWCNT。以前，已发现暴露于高温下的MWCNT（MWCNT-HT）或与氮合成的MWCNT（MWCNT-ND）引起减弱的毒性。但是，它们的遗传毒性和致癌潜力尚不清楚。我们的目的是测量与这两种物理化学改变的MWCNT相比，MWCNT-7在人肺上皮细胞（BEAS-2B和SAEC）中的遗传毒性。对于每种MWCNT材料，观察到细胞核中单个纳米管的剂量依赖性分配，并且对于MWCNT-7最大。暴露于每个MWCNT会导致具有多极和单极纺锤体形态以及分散的中心体的有丝分裂像差显着增加。纺锤极的定量分析表明，每个MWCNT的中心体碎片从0.024–2.4μg/ mL显着增加。在每个MWCNT-7，HT和ND的剂量反应中都检测到显着的非整倍性；最高剂量24μg/ mL分别产生67％，61％和55％。染色体分析表明，在每个剂量下，每个MWCNT的着丝粒破碎和易位明显增加。在BEAS-2B中暴露于MWCNT-7，ND和/或HT 24小时后，在细胞周期的G1 / S期发生了明显的停滞，而MWCNT-ND也诱导了G2的阻滞。暴露于每个MWCNT 24小时的主要SAEC在G1和G2相中引起明显更大的阻滞。然而，暴露后72小时，SAEC在G1 / S期被捕。最后，在接触0.024μg/ mL MWCNT-HT和ND一个月后，观察到克隆生长显着增加。尽管MWCNT-HT和ND引起的基因毒性发生率较低，但所有三种MWCNT都会引起相同类型的有丝分裂和染色体破坏。其他纳米材料尚未观察到染色体断裂和易位。由于体外遗传毒性与体内遗传毒性反应相关，因此在原发性人类肺细胞中的这些研究可预测暴露人群的遗传毒性潜能。暴露于每个MWCNT 24小时的主要SAEC在G1和G2相中引起明显更大的阻滞。然而，暴露后72小时，SAEC在G1 / S期被捕。最后，在接触0.024μg/ mL MWCNT-HT和ND一个月后，观察到克隆生长显着增加。尽管MWCNT-HT和ND引起的基因毒性发生率较低，但所有三种MWCNT都会引起相同类型的有丝分裂和染色体破坏。其他纳米材料尚未观察到染色体断裂和易位。由于体外遗传毒性与体内遗传毒性反应相关，因此在原发性人类肺细胞中的这些研究可预测暴露人群的遗传毒性潜能。暴露于每个MWCNT 24小时的主要SAEC在G1和G2相中引起明显更大的阻滞。然而，暴露后72小时，SAEC在G1 / S期被捕。最后，在接触0.024μg/ mL MWCNT-HT和ND一个月后，观察到克隆生长显着增加。尽管MWCNT-HT和ND引起的基因毒性发生率较低，但所有三种MWCNT都会引起相同类型的有丝分裂和染色体破坏。其他纳米材料尚未观察到染色体断裂和易位。由于体外遗传毒性与体内遗传毒性反应相关，因此在原发性人类肺细胞中的这些研究可预测暴露人群的遗传毒性潜能。暴露于0.024μg/ mL MWCNT-HT＆ND后一个月，克隆生长显着增加。尽管MWCNT-HT和ND引起的基因毒性发生率较低，但所有三种MWCNT都会引起相同类型的有丝分裂和染色体破坏。其他纳米材料尚未观察到染色体断裂和易位。由于体外遗传毒性与体内遗传毒性反应相关，因此在原发性人类肺细胞中的这些研究可预测暴露人群的遗传毒性潜能。暴露于0.024μg/ mL MWCNT-HT＆ND后一个月，克隆生长显着增加。尽管MWCNT-HT和ND引起的基因毒性发生率较低，但所有三种MWCNT都会引起相同类型的有丝分裂和染色体破坏。其他纳米材料尚未观察到染色体断裂和易位。由于体外遗传毒性与体内遗传毒性反应相关，因此在原发性人类肺细胞中的这些研究可预测暴露人群的遗传毒性潜能。