title: Investigation of the pulmonary bioactivity of double-walled carbon nanotubes.
abstract: Double-walled carbon nanotubes (DWCNT) are a rather new and unexplored variety of carbon nanotubes. Previously conducted studies established that exposure to a variety of carbon nanotubes produced lung inflammation and fibrosis in mice after pharyngeal aspiration. However, the bioactivity of double-walled carbon nanotubes (DWCNT) has not been determined. In this study, the hypothesis that DWCNT would induce pulmonary toxicity was explored by analyzing the pulmonary bioactivity of DWCNT. To test this hypothesis, C57Bl/6 mice were exposed to DWCNT by pharyngeal aspiration. Mice underwent whole-lung lavage (WLL) to assess pulmonary inflammation and injury, and lung tissue was examined histologically for development of pulmonary disease as a function of dose and time. The results showed that DWCNT exposure produced a dose-dependent increase in WLL polymorphonuclear leukocytes (PMN), indicating that DWCNT exposure initiated pulmonary inflammation. DWCNT exposure also produced a dose-dependent rise in lactate dehydrogenase (LDH) activity, as well as albumin levels, in WLL fluid, indicating that DWCNT exposure promoted cytotoxicity as well as decreases in the integrity of the blood-gas barrier in the lung, respectively. In addition, at 7 and 56 d postexposure, the presence of significant alveolitis and fibrosis was noted in mice exposed to 40 μg/mouse DWCNT. In conclusion, this study provides insight into previously uninvestigated pulmonary bioactivity of DWCNT exposure. Data indicate that DWCNT exposure promotes inflammation, injury, and fibrosis in the lung.
authors.affiliation: a National Institute for Occupational Safety and Health, Health Effects Laboratory Division , Pathology and Physiology Research Branch , Morgantown , West Virginia , USA.
authors.forename: Tina M
authors.initials: TM
authors.lastname: Sager
authors.forename: Michael W
authors.initials: MW
authors.lastname: Wolfarth
authors.forename: Lori A
authors.initials: LA
authors.lastname: Battelli
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Leonard
authors.forename: Michael
authors.initials: M
authors.lastname: Andrew
authors.forename: Thomas
authors.initials: T
authors.lastname: Steinbach
authors.forename: Morinobu
authors.initials: M
authors.lastname: Endo
authors.forename: Shuji
authors.initials: S
authors.lastname: Tsuruoka
authors.forename: Dale W
authors.initials: DW
authors.lastname: Porter
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
mesh_terms: D000818:Animals; D015824:Blood-Air Barrier / Q000187:drug effects* / Q000473:pathology; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D019570:Inhalation Exposure / Q000009:adverse effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D037742:Nanotubes, Carbon / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
chemical_list: D037742:Nanotubes, Carbon; D007770:L-Lactate Dehydrogenase