Different functionalizations of MWCNT influence transformation potential in primary human lung epithelial cells.
Stueckle-TA; Derk-R; Chen-M; Castranova-V; Rojanasakul-Y; Wang-L
Toxicologist 2014 Mar; 138(1):154
MWCNT have received increased scrutiny for potential human health impacts based on their fibrogenicity and promotion of pulmonary carcinogenesis. Functionalized CNT (fCNT) development has intensified to improve surface activity in technological applications, and potentially reduce toxicity. Subchronic in vitro CNT exposure causes neoplastic-like transformation; however, tumorigenic risk associated with fMWCNT exposure in human lung epithelium is presently unknown. To identify early steps in fMWCNT-induced cell transformation, this study hypothesized that different functional groups of MWCNT determine their neoplastic transformation potential in primary human small airway epithelial cells (SAECs). Cells were continuously exposed (0.06mg/cm2) to dispersed pure (pMWCNT), carboxylated (cMWCNT), and aminated MWCNT (nMWCNT) for 8 and 12 weeks. Dispersed ultrafine carbon black (UFCB) and crocidolite asbestos served as controls. Exposed cells were assessed for several established cancer hallmarks and morphological transformation. UFCB and pMWCNT cells at 48h and all MWCNT cells at 6d post-treatment exhibited significant increased proliferation compared to controls. UFCB exposure stimulated significant invasion and migration behavior while pMWCNT and cMWCNT showed moderate significant increases; however, these trends disappeared at 6d post-exposure. Conversely, nMWCNT displayed the largest significant increase in colony formation potential while UFCB showed a moderate significant increase. All other treatments did not differ from controls. UFCB and nMWCNT cells exhibited increased foci frequency, indicative of neoplastic transformation, compared to all other treatments. In summary, surface charge characteristics of carbon nanoparticles can impact transient, early neoplastic transformation events in vitro following occupationally relevant exposures.
Toxicology; Cell-function; Cellular-function; Cell-damage; Nanotechnology; Lung; Exposure-levels; Pulmonary-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Carcinogenesis; In-vitro-study
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona