Genotoxicity of carbon nanofibers: are they potentially more or less dangerous than carbon nanotubes or asbestos?
Kisin-ER; Murray-AR; Sargent-L; Lowry-D; Chirila-M; Siegrist-KJ; Schwegler-Berry-D; Leonard-S; Castranova-V; Fadeel-B; Kagan-VE; Shvedova-AA
Toxicol Appl Pharmacol 2011 Apr; 252(1):1-10
The production of carbon nanofibers and nanotubes (CNF/CNT) and their composite products is increasing globally. CNF are generating great interest in industrial sectors such as energy production and electronics, where alternative materials may have limited performance or are produced at a much higher cost. However, despite the increasing industrial use of carbon nanofibers, information on their potential adverse health effects is limited. In the current study, we examine the cytotoxic and genotoxic potential of carbon-based nanofibers (Pyrograf (R)-III) and compare this material with the effects of asbestos fibers (crocidolite) or single-walled carbon nanotubes (SWCNT). The genotoxic effects in the lung fibroblast (V79) cell line were examined using two complementary assays: the comet assay and micronucleus (MN) test. In addition, we utilized fluorescence in situ hybridization to detect the chromatin pan-centromeric signals within the MN indicating their origin by aneugenic (chromosomal malsegregation) or clastogenic (chromosome breakage) mechanisms. Cytotoxicity tests revealed a concentration- and time-dependent loss of V79 cell viability after exposure to all tested materials in the following sequence: asbestos>CNF>SWCNT. Additionally, cellular uptake and generation of oxygen radicals was seen in the murine RAW264.7 macrophages following exposure to CNF or asbestos but not after administration of SWCNT. DNA damage and MN induction were found after exposure to all tested materials with the strongest effect seen for CNF. Finally, we demonstrated that CNF induced predominately centromere-positive MN in primary human small airway epithelial cells (SAEC) indicating aneugenic events. Further investigations are warranted to elucidate the possible mechanisms involved in CNF-induced genotoxicity.
Carcinogens; Cell-biology; Cellular-reactions; Cytotoxic-effects; Fibrogenesis; Genotoxic-effects; Lung-fibrosis; Nanotechnology; Pulmonary-system; Respiratory-hypersensitivity; Respiratory-irritants;
Author Keywords: Carbon nanofibers; Genotoxicity; Oxidative stress; DNA damage; Cytotoxicity
A.A. Shvedova, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
Toxicology and Applied Pharmacology
University of Pittsburgh at Pittsburgh