Different Cellular Response of Human Mesothelial Cell MeT-5A to Short-Term and Long-Term Multiwalled Carbon Nanotubes Exposure

Abstract

Despite being a commercially important product, multiwalled carbon nanotubes (MWCNTs) continue to raise concerns over human health due to their structural similarity to asbestos. Indeed, exposure to MWCNT has been shown to induce lung cancer and even mesothelioma, but contradictory results also exist. To clarify the potentially carcinogenic effects of rigid and rod-like MWCNT and to elucidate the underlying mechanisms, the effects of MWCNT on human mesothelial cell MeT-5A were examined throughout 3 months of continuous exposure, including cytotoxicity, genotoxicity, and cell motility. It was found that MWCNT did not affect MeT-5A cell proliferation at 10 μg/cm2 within 72 h treatment, but under the same condition, MWCNT induced genotoxicity and perturbed cell motility. In addition, MeT-5A cells demonstrated different cellular responses to MWCNT after short-term and long-term exposure. Taken together, our results indicated a possible carcinogenic potential for MWCNT after long-term treatment, in which Annexin family proteins might be involved.

Biocompatibility and Carcinogenicity of Carbon Nanotubes as Biomaterials

“…SSC values have been reported to increase for crocidolite asbestos, but not for MWCNTs, and the diameter and rigidity of CNTs and crocidolite affect their uptake into cells [19]. Ju et al [23] conducted an experiment by which MWCNTs were added to human pleural mesothelial cells (MeT-5A). MWCNTs were added in concentrations ranging from 1.25 to 40 µg/cm 2 , and the cell viability showed concentration-dependent suppression at 24 h after treatment.…”

Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System

“…Similar results have been seen in in vitro studies. Long-term exposure of primary human airway epithelial cells (SAECs) to commercial short SWCNTs (CNI, Houston, TX, USA), long Mitsui-7 MWCNTs (Mitsui & Co., Ltd., Tokyo, Japan) and Crocidolite, and mesothelial MeT-5A cells exposed to commercial long MWCNTs (Sigma-Aldrich, St Louis, MO, USA) have demonstrated a substantial increase in DNA damage in γH2A.X foci and p53 dysregulation [ 54 , 78 ].…”

“…The transformation potential in vitro has been documented in different studies. After long-term exposure to commercial long MWCNTs (Sigma-Aldrich, St Louis, MO, USA), mesothelial MeT-5A cells showed features resembling a malignant transformation process and specifically an increase in cell proliferation and invasion capacity, morphology change, and DNA damage [ 78 ].…”

Carbon Nanotubes and Other Engineered Nanoparticles Induced Pathophysiology on Mesothelial Cells and Mesothelial Membranes

“…On the other hand, Annexins 2 and 6 decreased by 30 d and markedly increased at approximately the 90 d timepoint. Subsequently, Annexin 1 was validated to contribute in cell migration, as siRNA knockdown significantly reduced the migratory potential of transfected MeT5A cells in a wound healing assay (Ju et al, 2017 ). In summary, CNTs, similarly to asbestos fibers, were demonstrated to induce malignant-like behavior in chronically exposed mesothelial cells that was driven by a gene signaling network involving H-Ras/ERK, MMP-2, Cortactin, Integrins and Annexins 1, 2, 5, and 6.…”