Potential carcinogenicity of carbon nanotubes.
Rojanasakul-Y; Lu-Y; Luanpitpong-S; Castranova-V; Pongrakhananon-V; Wang-L
Toxicologist 2011 Mar; 120(Suppl 2):254
Carbon nanotubes (CNT) have increasing been used for wide applications with a potential for human exposure. Concerns about the potential carcinogenicity of CNT have been raised since CNT exhibit a bio-persistence and a fibrous morphology similar to asbestos which is a known carcinogen. However, there is neither clear knowledge nor a practical method to assess this potential. In this study, we developed an in vitro chronic exposure model combined with in vivo xenograft model to address these needs. Non-tumorigenic human lung epithelial BEAS-2B cells were continuously exposed to a sub-cytotoxic concentration (0.04 ug/ml or 0.02 ug/cm2 exposed area) of single-walled CNT (SWCNT) in culture. Phenotypic changes were observed in SWCNT-treated cells 20 weeks post-exposure such as formation of cell mounds and accelerated cell growth. SWCNT-treated cells were subsequently analyzed for malignant properties including colony formation, cell migration and invasive properties. Significant positive results were observed from SWCNT-treated cells in all above studies compared to passage-matched control cells. In vivo tumorigenesis study was performed by subcutaneously injecting the transformed cells into nude mice. Consistent with the in vitro cell transformation results, the in vivo results showed large tumor formation at the injection site in mice receiving SWCNT-transformed cells, whereas mice receiving control cells showed no tumor formation. These studies indicate that long-term/low dose exposure of human lung epithelial cells to SWCNT induced malignant transformation of the cells which induced tumor formation in vivo. These results suggest a potential carcinogenic effect of SWCNT. The described cell model system could potentially be used as a predictive model for carcinogenicity testing of nanomaterials.
Biological-effects; Cancer; Carcinogenicity; Cell-biology; Cell-function; Cell-metabolism; Cell-morphology; Cell-transformation; Cellular-reactions; Exposure-assessment; Humans; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lung-cancer; Lung-cells; Lung-disease; Lung-disorders; Lung-irritants; Medical-research; 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