title: Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons.
abstract: 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 1 yr after pharyngeal aspiration. In addition, we compared pulmonary responses to SWCNT by bolus dosing through pharyngeal aspiration and inhalation 5 h/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 1 yr postexposure, whereas 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, whereas SWCNT were the most fibrogenic of these three particles. Furthermore, 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 yr postexposure 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.
authors.affiliation: NIOSH, CDC, 1095 Willowdale Rd., Morgantown, WV 26505. ats1@cdc.gov.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Shvedova
authors.forename: Naveena
authors.initials: N
authors.lastname: Yanamala
authors.forename: Elena R
authors.initials: ER
authors.lastname: Kisin
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Tkach
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Murray
authors.forename: Ann
authors.initials: A
authors.lastname: Hubbs
authors.forename: Madalina M
authors.initials: MM
authors.lastname: Chirila
authors.forename: Phouthone
authors.initials: P
authors.lastname: Keohavong
authors.forename: Lyudmila P
authors.initials: LP
authors.lastname: Sycheva
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001194:Asbestos / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D001996:Bronchopneumonia / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D002244:Carbon / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D005260:Female; D011905:Genes, ras / Q000235:genetics; D019570:Inhalation Exposure / Q000009:adverse effects*; D008199:Lymphadenitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D037742:Nanotubes, Carbon / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D013059:Spectrum Analysis, Raman; D013995:Time
chemical_list: D002273:Carcinogens; D037742:Nanotubes, Carbon; D001194:Asbestos; D002244:Carbon
keywords: fibrosis; genotoxicity; inflammation; long-term postexposure; nanoparticles