In vitro assessment of potential tumorgenicity of chronic SWCNT and MWCNT exposure to lung epithelium.
Stueckle-TA; Mishra-A; Derk-R; Rojanasakul-Y; Castranova-V; Wang-L
Toxicologist 2011 Mar; 120(Suppl 2):253
Carbon nanotube use in multiple consumer and industrial products has resulted in increased concern for long-term risks to human health. Recent in vivo studies suggest that inhaled carbon nanotubes induce interstitial fibrosis and persist in exposed lung tissues. No clear evidence or experimental model exists to assess whether longterm pulmonary exposures of CNT to lung tissue results in transformed cells expressing a tumorigenic phenotype. This study tested the hypothesis that chronic exposure to dispersed carbon nanotubes induces neoplastic transformation in lung epithelial cells in vitro. Small airway lung epithelial cells were exposed for 25 weeks to either dispersed single wall (D-SWCNT) or multi-wall (D-MWCNT) carbon nanotubes at non-cytotoxic levels (0.02 ug/cm2). Dispersed ultra fine carbon black (D-CB) and asbestsos (ABS) served as negative and positive controls. Following exposure each treatment was evaluated for tumorigenic phenotypes using cell proliferation, cell invasion and colony formation assays in untreated media. D-SWCNT exhibited a significant 1.5-fold increase in cell proliferation compared to passage control cells while D-MWCNT and D-CB showed a modest increase. In addition, D-SWCNT cells displayed significantly greater invasive potential than DMWCNT, ABS and passage control. Lastly, a tumor formation assay resulted in DSWCNT cells possessing a significant 5-fold increase in the number of colonies formed above controls while D-MWCNT and D-CB exhibited only a 1.5-fold increase. Our chronic, low dose in vitro exposure model suggested that D-SWCNT exposure caused neoplastic transformation resulting in a tumorigenic phenotype while D-MWCNT exposure displayed less malignant potential. In conclusion, use of in vitro screening methods, along with comparable in vivo data, can assist in investigation of tumorigenic risks associated with carbon nanotube and other nanomaterial exposures.
Biological-effects; Exposure-assessment; Inhalation-studies; Laboratory-testing; Lung-cells; Lung-fibrosis; Lung-irritants; Nanotechnology; Physiological-effects; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Risk-analysis; Risk-factors; Statistical-analysis
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC