Thumbnail
Access Restriction
Open

Author Frank, Evan A. ♦ Carreira, Vinicius S. ♦ Shanmukhappa, Kumar ♦ Medvedovic, Mario ♦ Prows, Daniel R. ♦ Yadav, Jagjit S.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ CARBON NANOTUBES ♦ GENES ♦ GENETICS ♦ LEUKOCYTES ♦ LUNGS ♦ MICE ♦ NANOPARTICLES ♦ PATHOLOGY ♦ SENSITIVITY ♦ STRAINS
Abstract The risk of human exposure to fiber nanoparticles has risen in recent years due to increases in the manufacture and utilization of carbon nanotubes (CNTs). CNTs are present as airborne particulates in occupational settings and their hazard potential has been demonstrated in experimental lung exposure studies using inbred mouse strains. However, it is not known whether different inbred strains differ in lung responses to CNTs by virtue of their genetics. In this work, common inbred strains (BALB/c, C57Bl/6, DBA/2, and C3H/He) were exposed to CNTs via oropharyngeal aspiration and lung histology and bronchoalveolar lavage (BAL) samples were evaluated over 28 days with the objective of evaluating sensitivity/resistance among strains. C57Bl/6 mice developed significantly more extensive type II pneumocyte (T2P) hyperplasia and alveolar infiltrate compared to DBA/2 mice, which were resistant. Surprisingly, DBA/2 but not C57Bl/6 mice were extremely sensitive to increases in leukocytes recovered in BAL fluid. Underlying global gene expression patterns in the two strains were compared using mRNA sequencing to investigate regulatory networks associated with the different effects. The impact of exposure on gene networks regulating various aspects of immune response and cell survival was limited in DBA/2 mice compared to C57Bl/6. Investigation of B6D2F1 (C57Bl/6 × DBA/2 hybrid) mice demonstrated inheritance of sensitivity to CNT exposures in regard to toxicologic lung pathology and BAL leukocyte accumulations. These findings demonstrate a genetic basis of susceptibility to CNT particle exposures and both inform the use of inbred mouse models and suggest the likelihood of differences in genetic susceptibility among humans. - Highlights: • Strain-specific effects followed instilled lung exposure to thin, tangled MWCNTS in mice. • Exposed C57Bl/6 exhibits more pronounced lung pathology and proinflammatory signaling. • Exposed DBA/2 responds with highly sensitive increases in leukocytes in lavage samples • Genetic background is shown to play a role in nature and severity of adverse effects.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2017-07-15
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 327


Open content in new tab

   Open content in new tab