Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons.
Shvedova AA; Yanamala N; Kisin ER; Tkach AV; Murray AR; Hubbs A; Chirila MM; Keohavong P; Sycheva LP; Kagan VE; Castranova V
Am J Physiol, Lung Cell Mol Physiol 2014 Jan; 306(2):L170-L182
The hallmark geometric feature of single-walled carbon nanotubes (SWCNT) and carbon nanofibers (CNF) - high length to width ratio - makes them similar to a hazardous agent - asbestos. Very limited data are available concerning long-term effects of pulmonary exposure to SWCNT or CNF. Here we compared inflammatory, fibrogenic and genotoxic effects of CNF, SWCNT or asbestos in mice one year after pharyngeal aspiration. In addition, we compared pulmonary responses to SWCNT by bolus dosing through pharyngeal aspiration and inhalation 5h/day for 4 days, to evaluate the effect of dose rate. The aspiration studies showed that, these particles can be visualized in the lung at one year post-exposure, while some translocate to lymphatics. All these particles induced chronic bronchopneumonia and lymphadenitis, accompanied by pulmonary fibrosis. CNF and asbestos were found to promote the greatest degree of inflammation, followed by SWCNT, while SWCNT were the most fibrogenic of these three particles. Further, SWCNT induced cytogenetic alterations seen as micronuclei formation and nuclear protrusions in vivo. Importantly, inhalation exposure to SWCNT showed significantly greater inflammatory, fibrotic and genotoxic effects than bolus pharyngeal aspiration. Finally, SWCNT and CNF, but not asbestos exposures, increased the incidence of K-ras oncogene mutations in the lung. No increased lung tumor incidence occurred after 1 year post exposure to SWCNT, CNF and asbestos. Overall, our data suggest that long-term pulmonary toxicity of SWCNT, CNF and asbestos - is defined not only by their chemical composition but also by the specific surface area and type of exposure.
Nanotechnology; Asbestos-fibers; Lung; Lung-cells; Lung-fibrosis; Lung-disorders; Exposure-assessment; Fibrosis; Pulmonary-system-disorders; Respiratory-system-disorders; Fibrogenesis; Genotoxic-effects; Immune-reaction; Immune-system; Pulmonary-function; Exposure-assessment; Cytotoxic-effects; Long-term-exposure;
Author Keywords: nanoparticles; long-term post exposure; inflammation; fibrosis; genotoxicity
Dr. Anna A. Shvedova, NIOSH, CDC, 1095 Willowdale Rd, Morgantown, WV 26505 USA
American Journal of Physiology: Lung Cellular and Molecular Physiology
University of Pittsburgh at Pittsburgh