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The Genetic Heterogeneity among Different Mouse Strains Impacts the Lung Injury Potential of Multiwalled Carbon Nanotubes.

ABSTRACT: Genetic variation constitutes an important variable impacting the susceptibility to inhalable toxic substances and air pollutants, as reflected by epidemiological studies in humans and differences among animal strains. While multiwalled carbon nanotubes (MWCNTs) are capable of causing lung fibrosis in rodents, it is unclear to what extent the genetic variation in different mouse strains influence the outcome. Four inbred mouse strains, including C57Bl/6, Balb/c, NOD/ShiLtJ, and A/J, to test the pro-fibrogenic effects of a library of MWCNTs in vitro and in vivo are chosen. Ex vivo analysis of IL-1? production in bone marrow-derived macrophages (BMDMs) as molecular initiating event (MIE) is performed. The order of cytokine production (Balb/c > A/J > C57Bl/6 > NOD/ShiLtJ) in BMDMs is also duplicated during assessment of IL-1? production in the bronchoalveolar lavage fluid of the same mouse strains 40 h after oropharyngeal instillation of a representative MWCNT. Animal test after 21 d also confirms a similar hierarchy in TGF-?1 production and collagen deposition in the lung. Statistical analysis confirms a correlation between IL-1? production in BMDM and the lung fibrosis. All considered, these data demonstrate that genetic background indeed plays a major role in determining the pro-fibrogenic response to MWCNTs in the lung.

SUBMITTER: Wang X

PROVIDER: S-EPMC5581261 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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The Genetic Heterogeneity among Different Mouse Strains Impacts the Lung Injury Potential of Multiwalled Carbon Nanotubes.

Wang Xiang X Liao Yu-Pei YP Telesca Donatello D Chang Chong Hyun CH Xia Tian T Nel André E AE

Small (Weinheim an der Bergstrasse, Germany) 20170705 33

Genetic variation constitutes an important variable impacting the susceptibility to inhalable toxic substances and air pollutants, as reflected by epidemiological studies in humans and differences among animal strains. While multiwalled carbon nanotubes (MWCNTs) are capable of causing lung fibrosis in rodents, it is unclear to what extent the genetic variation in different mouse strains influence the outcome. Four inbred mouse strains, including C57Bl/6, Balb/c, NOD/ShiLtJ, and A/J, to test the ...[more]

PMID: 28677920

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Project description:The industrial use and widespread application of carbon-based nanomaterials have caused a rapid increase in their production over the last decades. However, toxicity of these materials is not fully known and is still being investigated for potential human and ecological health risks. Detecting carbon-based nanomaterials in the environment using current analytical methods is problematic, making environmental fate and transport modeling a practical way to estimate environmental concentrations and assess potential ecological risks. The Water Quality Analysis Simulation Program 8 (WASP8) is a dynamic, spatially resolved fate and transport model for simulating exposure concentrations in surface waters and sediments. Recently, WASP has been updated to incorporate processes for simulating the fate and transport of nanomaterials including heteroaggregation and phototransformation. This study examines the fate and transport of multiwalled carbon nanotubes (MWCNT), graphene oxide (GO) and reduced graphene oxide (rGO) in four aquatic ecosystems in the southeastern United States. Sites include a seepage lake, a coastal plains river, a piedmont river and an unstratified, wetland lake. A hypothetical 50-year release is simulated for each site-nanomaterial pair to analyze nanomaterial distribution between the water column and sediments. For all nanomaterials, 99% of the mass loaded moves though systems of high and low residence times without being heteroaggregated and deposited in the sediments. However, significant accumulation in the sediments does occur over longer periods of time. Results show that GO and rGO had the highest mass fraction in the water column of all four sites. MWCNT were found predominantly in the sediments of the piedmont river and seepage lake but were almost entirely contained in the water column of the coastal plains river and wetland lake. Simulated recovery periods following the release estimate 37+?years for lakes and 1-4?years for rivers to reduce sediment nanomaterial concentrations by 50% suggesting that carbon-based nanomaterials have the potential for long-term ecological effects.

Dataset Information

The Genetic Heterogeneity among Different Mouse Strains Impacts the Lung Injury Potential of Multiwalled Carbon Nanotubes.

Publications

The Genetic Heterogeneity among Different Mouse Strains Impacts the Lung Injury Potential of Multiwalled Carbon Nanotubes.

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