T.A. Stueckle, D.C. Davidson, R. Derk, P. Gracheck, N. Wu, Y. Rojanasakul, L. Wang
National Institute for Occupational Safety and Health, United States
pp. 574 - 577
Keywords: carbon nanotubes, cell transformation, functionalization, in vitro model, mesothelium
Multi-walled carbon nanotubes (MWCNTs) are characterized by asbestos-like fiber morphology and surface chemistries. Physicochemical properties of MWCNTs that influence pleural mesothelioma potential are unknown, but critically needed to enhance safe-by-design nanotechnology. We hypothesized that surface functionalization of MWCNT would affect human mesothelial cell neoplastic transformation potential in a dose and time dependent manner. Cells were exposed to fully characterized prepared (pMWCNT), carboxylated (MW-COOH), aminated (MW-NH2) MWCNTs and asbestos (ASB) for 6 months at 0.002 and 0.02 µg/cm2, which are relevant to animal exposure. Each treatment group was assessed for several cancer hallmarks. Results indicated that 1) low dose MW-COOH and MW-NH2 exposure caused significant increases in cell proliferation compared to controls, starting at the third week and persisting over 6 months of exposure. 2) pMWCNT, MW-NH2 and ASB cells exhibited significantly greater numbers of soft agar colonies compared to controls starting at 4 months. 3) Only MW-COOH cells at 6 months exhibited a significant increase in invasion ability compared to all treatments. Lastly, ASB cells displayed the largest transformation frequency, while all fMWNCT treatments caused moderate effects. In summary, exposure dose, duration and type of surface functionalization determine MWCNT neoplastic transformation potential in pleural mesothelial cells.