title: Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis.
abstract: Nanomaterials are frontier technological products used in different manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon nanotubes (SWCNT) are finding numerous applications in electronics, aerospace devices, computers, and chemical, polymer, and pharmaceutical industries. SWCNT are relatively recently discovered members of the carbon allotropes that are similar in structure to fullerenes and graphite. Previously, we (47) have reported that pharyngeal aspiration of purified SWCNT by C57BL/6 mice caused dose-dependent granulomatous pneumonia, oxidative stress, acute inflammatory/cytokine responses, fibrosis, and decrease in pulmonary function. To avoid potential artifactual effects due to instillation/agglomeration associated with SWCNT, we conducted inhalation exposures using stable and uniform SWCNT dispersions obtained by a newly developed aerosolization technique (2). The inhalation of nonpurified SWCNT (iron content of 17.7% by weight) at 5 mg/m(3), 5 h/day for 4 days was compared with pharyngeal aspiration of varying doses (5-20 microg per mouse) of the same SWCNT. The chain of pathological events in both exposure routes was realized through synergized interactions of early inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and interstitial fibrosis. SWCNT inhalation was more effective than aspiration in causing inflammatory response, oxidative stress, collagen deposition, and fibrosis as well as mutations of K-ras gene locus in the lung of C57BL/6 mice.
authors.affiliation: Health Effects Laboratory Div., National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. ats1@cdc.gov
authors.forename: A A
authors.initials: AA
authors.lastname: Shvedova
authors.forename: E
authors.initials: E
authors.lastname: Kisin
authors.forename: A R
authors.initials: AR
authors.lastname: Murray
authors.forename: V J
authors.initials: VJ
authors.lastname: Johnson
authors.forename: O
authors.initials: O
authors.lastname: Gorelik
authors.forename: S
authors.initials: S
authors.lastname: Arepalli
authors.forename: A F
authors.initials: AF
authors.lastname: Hubbs
authors.forename: R R
authors.initials: RR
authors.lastname: Mercer
authors.forename: P
authors.initials: P
authors.lastname: Keohavong
authors.forename: N
authors.initials: N
authors.lastname: Sussman
authors.forename: J
authors.initials: J
authors.lastname: Jin
authors.forename: J
authors.initials: J
authors.lastname: Yin
authors.forename: S
authors.initials: S
authors.lastname: Stone
authors.forename: B T
authors.initials: BT
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Deye
authors.forename: A
authors.initials: A
authors.lastname: Maynard
authors.forename: V
authors.initials: V
authors.lastname: Castranova
authors.forename: P A
authors.initials: PA
authors.lastname: Baron
authors.forename: V E
authors.initials: VE
authors.lastname: Kagan
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage; D000818:Animals; D002244:Carbon / Q000494:pharmacology; D005260:Female; D005355:Fibrosis; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D037742:Nanotubes, Carbon / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects*; D010614:Pharynx; D012120:Respiration Disorders / Q000139:chemically induced*
chemical_list: D000336:Aerosols; D037742:Nanotubes, Carbon; D002244:Carbon