Carbon nanotubes have many promising applications. Although the low density and small size of carbon nanotubes makes respiratory exposures to workers likely during the production or use of commercial products, there is limited data on carcinogenicity of inhaled multi-walled carbon nanotubes (MWCNTs). We have therefore utilized a two stage initiation/promotion protocol to determine whether inhaled MWCNTs act as a complete carcinogen and/or promote the growth of cells with existing DNA damage. Six week old, male, B6C3F1 mice received a single dose of either methylcholanthrene (MC, 10 microg/g BW, i.p.) or vehicle (corn oil). One week after i.p. injections, mice were exposed by inhalation to MWCNTs (5 mg/m3, 5 hours/day, 5 days/week) or filtered air (controls) for a total of 15 days. The B6C3F1 mouse used in this study has intermediate susceptibility to lung carcinogenesis, and data obtained will have relevancy to existing human lung tumor data because lung tumors in this mouse strain exhibit many molecular and morphological similarities to human pulmonary tumors. At 17 months post-exposure, mice were euthanized and examined for lung tumor formation. Twenty percent of the filtered air controls, 33% of the MWCNT-exposed, and 50% of the MC followed by air-exposure, had a mean of one tumor per mouse. By contrast, 100% of the mice which received MC followed by MWCNTs had tumors with an average of 3.6 tumors per mouse. Additionally, mice exposed to MWCNTs or MC followed by MWCNTs had larger tumor volumes than their corresponding air-exposed control groups. Our preliminary data suggests that MWCNT exposure promotes the growth of spontaneously and chemically initiated lung cells, resulting in the development of lung tumors. In this study, mouse MWCNT lung burden approximates feasible human occupational exposures. Therefore, the results of this ongoing study indicate that caution should be used to limit human exposures to MWCNTs.
Toxicology; Nanotechnology; Laboratory-animals; Laboratory-techniques; Exposure-assessment; Exposure-levels; Pulmonary-disorders; Pulmonary-system; Lung-cancer; Dose-response; Lung-disorders; Cytotoxicity; Carcinogens; Inhalation-studies; Tumors; Lung-disease; DNA-damage; Cell-growth; Cell-alteration; Methyl-compounds; Lung-cells; Lung-burden; Cellular-reactions
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas