In the past years, several in vitro studies have addressed the pulmonary toxicity of multi-walled carbon nanotubes (MWCNT) and compared it with that caused by asbestos fibers, but their conclusions have been somewhat inconsistent and difficult to extrapolate to in vivo. Since cell coculture models were proposed to better represent the in vivo conditions than conventional monocultures, this work intended to compare the cytotoxicity and genotoxicity of MWCNT-7 (Mitsui-7) and crocidolite using A549 cells grown in a conventional monoculture or in coculture with THP-1 macrophages. Although a decrease in A549 viability was noted following exposure to a concentration range of MWCNT-7 and crocidolite, no viability change occurred in similarly exposed cocultures. Early events indicating epithelial to mesenchymal transition (EMT) were observed which could explain apoptosis resistance. The comet assay results were similar between the two models, being positive and negative for crocidolite and MWCNT-7, respectively. An increase in the micronucleus frequency was detected in the cocultured A549-treated cells with both materials, but not in the monoculture. On the other hand, exposure of A549 monocultures to MWCNT-7 induced a highly significant increase in nucleoplasmic bridges in which those were found embedded. Our overall results demonstrate that (i) both materials are cytotoxic and genotoxic, (ii) the presence of THP-1 macrophages upholds the viability of A549 cells and increases the aneugenic/clastogenic effects of both materials probably through EMT, and (iii) MWCNT-7 induces the formation of nucleoplasmic bridges in A549 cells.

中文翻译：

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MWCNT-7 和青石棉的细胞毒性和遗传毒性：肺泡上皮细胞与单核细胞衍生巨噬细胞共培养的评估。

在过去的几年中，一些体外研究已经解决了多壁碳纳米管（MWCNT）的肺毒性，并将其与石棉纤维引起的肺毒性进行了比较，但他们的结论有些不一致，难以推断到体内。由于提出的细胞共培养模型比传统的单一培养更好地代表体内条件，这项工作旨在比较 MWCNT-7 (Mitsui-7) 和青石棉的细胞毒性和遗传毒性，使用在传统单一培养或与 THP 共培养中生长的 A549 细胞-1 巨噬细胞。尽管在暴露于 MWCNT-7 和青石棉的浓度范围后注意到 A549 活力下降，但在类似暴露的共培养物中没有发生活力变化。观察到表明上皮间质转化 (EMT) 的早期事件，这可以解释细胞凋亡抗性。两种模型的彗星测定结果相似，分别对青石棉和 MWCNT-7 呈阳性和阴性。在用两种材料共培养的 A549 处理的细胞中检测到微核频率的增加，但在单一培养中没有。另一方面，将 A549 单一培养物暴露于 MWCNT-7 会导致发现嵌入的核质桥显着增加。我们的总体结果表明（i）两种材料都具有细胞毒性和遗传毒性，（ii）THP-1 巨噬细胞的存在维持了 A549 细胞的活力，并可能通过 EMT 增加了两种材料的致瘤/致畸作用，