Cell transformation potential of nano-cerium oxide (nCeO2), nano-ferric oxide (nFe2O3) compared to multiwalled carbon nanotubes (MWCNT).
Wang-L; Stueckle-TA; Demokritou-P; Chen-M; Derk-R; Luanpitpong-S; Ma-YJ; Castranova-V; Rojanasakul-Y
Toxicologist 2014 Mar; 138(1):214
Unique physicochemical properties of engineered nanomaterials (ENMs), including CNTs and metal oxides, are distinct from their micron-sized counterparts evidenced by their unique biological effects. Previous studies have suggested potential lung disorders induced by these EMNs. Recent animal study indicated cancer promotion by MWCNT. Our previous in vitro work showed subchronic single walled CNT or MWCNT exposure can cause human lung epithelial cell transformation which formed tumors when subcutaneously injected into mice. These findings raise ENM-induced carcinogenesis concerns due to rapid growth in ENM applications, including widely used nCeO2, nFe2O3 and MWCNT. The present work tested cell transformation potential of nCeO2 and nFe2O3 compared to MWCNT as a positive tumorigenic control. Primary human small airway epithelial cells were treated with a sub-toxic, low dose of ENMs (62.5 ng/cm2 of nCeO2 and nFe2O3, or 60 ng/cm2 of MWCNT), with albumin and saline as dispersant and no treatment controls, respectively. Cells were continuously exposed to ENM containing medium for 6 weeks. Following exposure, cells were assayed for cell transformation and cancer hallmark analysis. Increased cell proliferation suggested significant cell stimulation by nCeO2 and MWCNT. Next, nFe2O3 and MWCNT-treated cells formed soft agar colonies and significantly enhanced cell invasion which suggests their potential cell transformative effect. These results will guide future in vivo studies to confirm the observation and to assess the relevancy of our subchronic in vitro exposure model. Such an in vitro model may serve as a simple/fast/high throughput tool to screen countless ENM to predict cell transformation/carcinogenic potential and addresses a critical need in ENM risk assessment.
Toxicology; Cell-function; Cellular-function; Cell-damage; Exposure-levels; Pathology; Biomarkers; Risk-factors; Immunology; Immune-system; Pathogenesis; Diseases; Neurotoxins; Chemical-properties; Nanotechnology; Oxides; Metal-compounds; Metal-oxides; Metallic-compounds; Biological-effects; Lung-disorders; Cancer; In-vitro-study; Tumors; Carcinogenesis
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona