Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice

Justyna Modrzynska, Trine Berthing, Gitte Ravn-Haren, Nicklas Raun Jacobsen, Ingrid Konow Weydahl, Katrin Löschner, Alicja Mortensen, Anne Thoustrup Saber, Ulla Vogel*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Background
Little is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during pulmonary inflammation and acute-phase response. To address this, we evaluated induction of pulmonary inflammation, pulmonary and hepatic acute-phase response and genotoxicity following exposure to titanium dioxide (TiO2), cerium oxide (CeO2) or CB NPs. Female C57BL/6 mice were exposed by intratracheal instillation, intravenous injection or oral gavage to a single dose of 162 μg NPs/mouse and terminated 1, 28 or 180 days post-exposure alongside vehicle control.

Results
Liver DNA damage assessed by the Comet Assay was observed after intravenous injection and intratracheal instillation of CB NPs but not after exposure to TiO2 or CeO2. Intratracheal exposure to NPs resulted in pulmonary inflammation in terms of increased neutrophils influx for all NPs 1 and 28 days post-exposure. Persistent pulmonary acute phase response was detected for all NPs at all three time points while only a transient induction of hepatic acute phase response was observed. All 3 materials were detected in the liver by enhanced darkfield microscopy up to 180 days post-exposure. In contrast to TiO2 and CeO2 NPs, CB NPs generated ROS in an acellular assay.

Conclusions
Our results suggest that the observed hepatic DNA damage following intravenous and intratracheal dosing with CB NPs was caused by the presence of translocated, ROS-generating, particles detected in the liver rather than by the secondary effects of pulmonary inflammation or hepatic acute phase response.
Original languageEnglish
JournalParticle and Fibre Toxicology
Volume15
Issue number2
Number of pages12
ISSN1743-8977
DOIs
Publication statusPublished - 2018

Cite this

Modrzynska, Justyna ; Berthing, Trine ; Ravn-Haren, Gitte ; Raun Jacobsen, Nicklas ; Konow Weydahl, Ingrid ; Löschner, Katrin ; Mortensen, Alicja ; Saber, Anne Thoustrup ; Vogel, Ulla. / Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice. In: Particle and Fibre Toxicology. 2018 ; Vol. 15, No. 2.
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title = "Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice",
abstract = "BackgroundLittle is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during pulmonary inflammation and acute-phase response. To address this, we evaluated induction of pulmonary inflammation, pulmonary and hepatic acute-phase response and genotoxicity following exposure to titanium dioxide (TiO2), cerium oxide (CeO2) or CB NPs. Female C57BL/6 mice were exposed by intratracheal instillation, intravenous injection or oral gavage to a single dose of 162 μg NPs/mouse and terminated 1, 28 or 180 days post-exposure alongside vehicle control.ResultsLiver DNA damage assessed by the Comet Assay was observed after intravenous injection and intratracheal instillation of CB NPs but not after exposure to TiO2 or CeO2. Intratracheal exposure to NPs resulted in pulmonary inflammation in terms of increased neutrophils influx for all NPs 1 and 28 days post-exposure. Persistent pulmonary acute phase response was detected for all NPs at all three time points while only a transient induction of hepatic acute phase response was observed. All 3 materials were detected in the liver by enhanced darkfield microscopy up to 180 days post-exposure. In contrast to TiO2 and CeO2 NPs, CB NPs generated ROS in an acellular assay.ConclusionsOur results suggest that the observed hepatic DNA damage following intravenous and intratracheal dosing with CB NPs was caused by the presence of translocated, ROS-generating, particles detected in the liver rather than by the secondary effects of pulmonary inflammation or hepatic acute phase response.",
author = "Justyna Modrzynska and Trine Berthing and Gitte Ravn-Haren and {Raun Jacobsen}, Nicklas and {Konow Weydahl}, Ingrid and Katrin L{\"o}schner and Alicja Mortensen and Saber, {Anne Thoustrup} and Ulla Vogel",
year = "2018",
doi = "10.1186/s12989-017-0238-9",
language = "English",
volume = "15",
journal = "Particle and Fibre Toxicology",
issn = "1743-8977",
publisher = "BioMed Central",
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Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice. / Modrzynska, Justyna; Berthing, Trine; Ravn-Haren, Gitte; Raun Jacobsen, Nicklas; Konow Weydahl, Ingrid; Löschner, Katrin; Mortensen, Alicja; Saber, Anne Thoustrup; Vogel, Ulla.

In: Particle and Fibre Toxicology, Vol. 15, No. 2, 2018.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice

AU - Modrzynska, Justyna

AU - Berthing, Trine

AU - Ravn-Haren, Gitte

AU - Raun Jacobsen, Nicklas

AU - Konow Weydahl, Ingrid

AU - Löschner, Katrin

AU - Mortensen, Alicja

AU - Saber, Anne Thoustrup

AU - Vogel, Ulla

PY - 2018

Y1 - 2018

N2 - BackgroundLittle is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during pulmonary inflammation and acute-phase response. To address this, we evaluated induction of pulmonary inflammation, pulmonary and hepatic acute-phase response and genotoxicity following exposure to titanium dioxide (TiO2), cerium oxide (CeO2) or CB NPs. Female C57BL/6 mice were exposed by intratracheal instillation, intravenous injection or oral gavage to a single dose of 162 μg NPs/mouse and terminated 1, 28 or 180 days post-exposure alongside vehicle control.ResultsLiver DNA damage assessed by the Comet Assay was observed after intravenous injection and intratracheal instillation of CB NPs but not after exposure to TiO2 or CeO2. Intratracheal exposure to NPs resulted in pulmonary inflammation in terms of increased neutrophils influx for all NPs 1 and 28 days post-exposure. Persistent pulmonary acute phase response was detected for all NPs at all three time points while only a transient induction of hepatic acute phase response was observed. All 3 materials were detected in the liver by enhanced darkfield microscopy up to 180 days post-exposure. In contrast to TiO2 and CeO2 NPs, CB NPs generated ROS in an acellular assay.ConclusionsOur results suggest that the observed hepatic DNA damage following intravenous and intratracheal dosing with CB NPs was caused by the presence of translocated, ROS-generating, particles detected in the liver rather than by the secondary effects of pulmonary inflammation or hepatic acute phase response.

AB - BackgroundLittle is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during pulmonary inflammation and acute-phase response. To address this, we evaluated induction of pulmonary inflammation, pulmonary and hepatic acute-phase response and genotoxicity following exposure to titanium dioxide (TiO2), cerium oxide (CeO2) or CB NPs. Female C57BL/6 mice were exposed by intratracheal instillation, intravenous injection or oral gavage to a single dose of 162 μg NPs/mouse and terminated 1, 28 or 180 days post-exposure alongside vehicle control.ResultsLiver DNA damage assessed by the Comet Assay was observed after intravenous injection and intratracheal instillation of CB NPs but not after exposure to TiO2 or CeO2. Intratracheal exposure to NPs resulted in pulmonary inflammation in terms of increased neutrophils influx for all NPs 1 and 28 days post-exposure. Persistent pulmonary acute phase response was detected for all NPs at all three time points while only a transient induction of hepatic acute phase response was observed. All 3 materials were detected in the liver by enhanced darkfield microscopy up to 180 days post-exposure. In contrast to TiO2 and CeO2 NPs, CB NPs generated ROS in an acellular assay.ConclusionsOur results suggest that the observed hepatic DNA damage following intravenous and intratracheal dosing with CB NPs was caused by the presence of translocated, ROS-generating, particles detected in the liver rather than by the secondary effects of pulmonary inflammation or hepatic acute phase response.

U2 - 10.1186/s12989-017-0238-9

DO - 10.1186/s12989-017-0238-9

M3 - Journal article

VL - 15

JO - Particle and Fibre Toxicology

JF - Particle and Fibre Toxicology

SN - 1743-8977

IS - 2

ER -