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7. MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

Author

Poulsen, Sarah S., Saber, Anne T., Williams, Andrew, Andersen, Ole, Købler, Carsten, Atluri, Rambabu, Pozzebon, Maria E., Mucelli, Stefano P., Simion, Monica, Rickerby, David, Mortensen, Alicja, Jackson, Petra, Kyjovska, Zdenka O., Mølhave, Kristian, Jacobsen, Nicklas R., Jensen, Keld A., Yauk, Carole L., Wallin, Håkan, Halappanavar, Sabina, and Vogel, Ulla

Published
2015
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10. Acute Phase Response as a Biological Mechanism‐of‐Action of (Nano)particle‐Induced Cardiovascular Disease

Author

Hadrup, Niels, primary, Zhernovkov, Vadim, additional, Jacobsen, Nicklas Raun, additional, Voss, Carola, additional, Strunz, Maximilian, additional, Ansari, Meshal, additional, Schiller, Herbert B., additional, Halappanavar, Sabina, additional, Poulsen, Sarah S., additional, Kholodenko, Boris, additional, Stoeger, Tobias, additional, Saber, Anne Thoustrup, additional, and Vogel, Ulla, additional

Published
2020
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12. Acute Phase Response as a Biological Mechanism-of-Action of (Nano)particle-Induced Cardiovascular Disease

Author

Hadrup, Niels, Zhernovkov, Vadim, Jacobsen, Nicklas Raun, Voss, Carola, Strunz, Maximilian, Ansari, Meshal, Schiller, Herbert B., Halappanavar, Sabina, Poulsen, Sarah S., Kholodenko, Boris, Stoeger, Tobias, Saber, Anne Thoustrup, Vogel, Ulla Birgitte, Hadrup, Niels, Zhernovkov, Vadim, Jacobsen, Nicklas Raun, Voss, Carola, Strunz, Maximilian, Ansari, Meshal, Schiller, Herbert B., Halappanavar, Sabina, Poulsen, Sarah S., Kholodenko, Boris, Stoeger, Tobias, Saber, Anne Thoustrup, and Vogel, Ulla Birgitte

Abstract

Inhaled nanoparticles constitute a potential health hazard due to their size-dependent lung deposition and large surface to mass ratio. Exposure to high levels contributes to the risk of developing respiratory and cardiovascular diseases, as well as of lung cancer. Particle-induced acute phase response may be an important mechanism of action of particle-induced cardiovascular disease. Here, the authors review new important scientific evidence showing causal relationships between inhalation of particle and nanomaterials, induction of acute phase response, and risk of cardiovascular disease. Particle-induced acute phase response provides a means for risk assessment of particle-induced cardiovascular disease and underscores cardiovascular disease as an occupational disease.

Published
2020

13. Physicochemical predictors of Multi-Walled Carbon Nanotube-induced pulmonary histopathology and toxicity one year after pulmonary deposition of 11 different Multi-Walled Carbon Nanotubes in mice

Author

Knudsen, Kristina B., Berthing, Trine, Jackson, Petra, Poulsen, Sarah S., Mortensen, Alicja, Jacobsen, Nicklas R., Skaug, Vidar, Szarek, Józef, Hougaard, Karin S., Wolff, Henrik, Wallin, Håkan, Vogel, Ulla Birgitte, Knudsen, Kristina B., Berthing, Trine, Jackson, Petra, Poulsen, Sarah S., Mortensen, Alicja, Jacobsen, Nicklas R., Skaug, Vidar, Szarek, Józef, Hougaard, Karin S., Wolff, Henrik, Wallin, Håkan, and Vogel, Ulla Birgitte

Published
2019

14. Physicochemical predictors of Multi-Walled Carbon Nanotube-induced pulmonary histopathology and toxicity one year after pulmonary deposition of 11 different Multi-Walled Carbon Nanotubes in mice

Author

Knudsen, Kristina B., primary, Berthing, Trine, additional, Jackson, Petra, additional, Poulsen, Sarah S., additional, Mortensen, Alicja, additional, Jacobsen, Nicklas R., additional, Skaug, Vidar, additional, Szarek, Józef, additional, Hougaard, Karin S., additional, Wolff, Henrik, additional, Wallin, Håkan, additional, and Vogel, Ulla, additional

Published
2018
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15. Corrigendum to “MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs” [Toxicol. Appl. Pharmacol., 284 (2015) 16–32]

Author

Poulsen, Sarah S., primary, Saber, Anne T., additional, Williams, Andrew, additional, Andersen, Ole, additional, Købler, Carsten, additional, Atluri, Rambabu, additional, Pozzebon, Maria E., additional, Mucelli, Stefano P., additional, Simion, Monica, additional, Rickerby, David, additional, Mortensen, Alicja, additional, Jackson, Petra, additional, Kyjovska, Zdenka O., additional, Mølhave, Kristian, additional, Jacobsen, Nicklas R., additional, Jensen, Keld A., additional, Yauk, Carole L., additional, Wallin, Håkan, additional, Halappanavar, Sabina, additional, and Vogel, Ulla, additional

Published
2018
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16. Corrigendum to “MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs” [Toxicol. Appl. Pharmacol., 284 (2015) 16–32]

Author

Poulsen, Sarah S., Saber, Anne T., Williams, Andrew, Andersen, Ole, Købler, Carsten, Atluri, Rambabu, Pozzebon, Maria E., Mucelli, Stefano P., Simion, Monica, Rickerby, David, Mortensen, Alicja, Jackson, Petra, Kyjovska, Zdenka O., Mølhave, Kristian, Jacobsen, Nicklas R., Jensen, Keld A., Yauk, Carole L., Wallin, Håkan, Halappanavar, Sabina, Vogel, Ulla Birgitte, Poulsen, Sarah S., Saber, Anne T., Williams, Andrew, Andersen, Ole, Købler, Carsten, Atluri, Rambabu, Pozzebon, Maria E., Mucelli, Stefano P., Simion, Monica, Rickerby, David, Mortensen, Alicja, Jackson, Petra, Kyjovska, Zdenka O., Mølhave, Kristian, Jacobsen, Nicklas R., Jensen, Keld A., Yauk, Carole L., Wallin, Håkan, Halappanavar, Sabina, and Vogel, Ulla Birgitte

Published
2018

19. Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity

Author

Poulsen, Sarah S., Jackson, Petra, Kling, Kirsten, Knudsen, Kristina B., Skaug, Vidar, Kyjovska, Zdenka O, Thomsen, Birthe L, Clausen, Per Axel, Atluri, Rambabu, Berthing, Trine, Bengtson, Stefan, Wolff, Henrik, Jensen, Keld A, Wallin, Håkan, Vogel, Ulla, Poulsen, Sarah S., Jackson, Petra, Kling, Kirsten, Knudsen, Kristina B., Skaug, Vidar, Kyjovska, Zdenka O, Thomsen, Birthe L, Clausen, Per Axel, Atluri, Rambabu, Berthing, Trine, Bengtson, Stefan, Wolff, Henrik, Jensen, Keld A, Wallin, Håkan, and Vogel, Ulla

Published
2016

20. Surface modification does not influence the genotoxic and inflammatory effects of TiO2 nanoparticles after pulmonary exposure by instillation in mice

Author

Wallin, Håkan, Kyjovska, Zdenka O., Poulsen, Sarah S., Jacobsen, Nicklas R., Saber, Anne T., Bengtson, Stefan, Jackson, Petra, Vogel, Ulla Birgitte, Wallin, Håkan, Kyjovska, Zdenka O., Poulsen, Sarah S., Jacobsen, Nicklas R., Saber, Anne T., Bengtson, Stefan, Jackson, Petra, and Vogel, Ulla Birgitte

Abstract

The influence of surface charge of nanomaterials on toxicological effects is not yet fully understood. We investigated the inflammatory response, the acute phase response and the genotoxic effect of two different titanium dioxide nanoparticles (TiO2 NPs) following a single intratracheal instillation. NRCWE-001 was unmodified rutile TiO2 with endogenous negative surface charge, whereas NRCWE-002 was surface modified to be positively charged. C57BL/6J BomTac mice received 18, 54 and 162 µg/mouse and were humanely killed 1, 3 and 28 days post-exposure. Vehicle controls were tested alongside for comparison. The cellular composition and protein concentration were determined in bronchoalveolar lavage (BAL) fluid as markers for an inflammatory response. Pulmonary and systemic genotoxicity was analysed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary and hepatic acute phase response was analysed by Saa3 mRNA levels in lung tissue or Saa1 mRNA levels in liver tissue by real-time quantitative polymerase chain reaction. Instillation of NRCWE-001 and -002 both induced a dose-dependent neutrophil influx into the lung lining fluid and Saa3 mRNA levels in lung tissue at all assessed time points. There was no statistically significant difference between NRCWE-001 and NRCWE-002. Exposure to both TiO2 NPs induced increased levels of DNA strand breaks in lung tissue at all doses 1 and 28 days post-exposure and NRCWE-002 at the low and middle dose 3 days post-exposure. The DNA strand break levels were statistically significantly different for NRCWE-001 and -002 for liver and for BAL cells, but no consistent pattern was observed. In conclusion, functionalisation of reactive negatively charged rutile TiO2 to positively charged did not consistently influence pulmonary toxicity of the studied TiO2 NPs.

Published
2016

22. Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity

Author

Poulsen, Sarah S., primary, Jackson, Petra, additional, Kling, Kirsten, additional, Knudsen, Kristina B., additional, Skaug, Vidar, additional, Kyjovska, Zdenka O., additional, Thomsen, Birthe L., additional, Clausen, Per Axel, additional, Atluri, Rambabu, additional, Berthing, Trine, additional, Bengtson, Stefan, additional, Wolff, Henrik, additional, Jensen, Keld A., additional, Wallin, Håkan, additional, and Vogel, Ulla, additional

Published
2016
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23. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

Author

Poulsen, Sarah S, Saber, Anne T, Mortensen, Alicja, Szarek, Józef, Wu, Dongmei, Williams, Andrew, Andersen, Ole, Jacobsen, Nicklas R, Yauk, Carole L, Wallin, Erik Håkan Richard, Halappanavar, Sabina, Vogel, Ulla, Poulsen, Sarah S, Saber, Anne T, Mortensen, Alicja, Szarek, Józef, Wu, Dongmei, Williams, Andrew, Andersen, Ole, Jacobsen, Nicklas R, Yauk, Carole L, Wallin, Erik Håkan Richard, Halappanavar, Sabina, and Vogel, Ulla

Published
2015

24. MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

Author

Poulsen, Sarah S, Saber, Anne T, Williams, Andrew, Andersen, Ole, Købler, Carsten, Atluri, Rambabu, Pozzebon, Maria E, Mucelli, Stefano P, Simion, Monica, Rickerby, David, Mortensen, Alicja, Jackson, Petra, Kyjovska, Zdenka O, Mølhave, Kristian, Jacobsen, Nicklas R, Jensen, Keld A, Yauk, Carole L, Wallin, Håkan, Halappanavar, Sabina, Vogel, Ulla, Poulsen, Sarah S, Saber, Anne T, Williams, Andrew, Andersen, Ole, Købler, Carsten, Atluri, Rambabu, Pozzebon, Maria E, Mucelli, Stefano P, Simion, Monica, Rickerby, David, Mortensen, Alicja, Jackson, Petra, Kyjovska, Zdenka O, Mølhave, Kristian, Jacobsen, Nicklas R, Jensen, Keld A, Yauk, Carole L, Wallin, Håkan, Halappanavar, Sabina, and Vogel, Ulla

Published
2015

25. Time-Dependent Subcellular Distribution and Effects of Carbon Nanotubes in Lungs of Mice

Author

Købler, Carsten, Poulsen, Sarah S, Saber, Anne T, Jacobsen, Nicklas R, Wallin, Håkan, Yauk, Carole L, Halappanavar, Sabina, Vogel, Ulla, Qvortrup, Klaus, Mølhave, Kristian, Købler, Carsten, Poulsen, Sarah S, Saber, Anne T, Jacobsen, Nicklas R, Wallin, Håkan, Yauk, Carole L, Halappanavar, Sabina, Vogel, Ulla, Qvortrup, Klaus, and Mølhave, Kristian

Published
2015

27. Surface modification does not influence the genotoxic and inflammatory effects of TiO2 nanoparticles after pulmonary exposure by instillation in mice.

Author

Wallin, Håkan, Kyjovska, Zdenka O., Poulsen, Sarah S., Jacobsen, Nicklas R., Saber, Anne T., Bengtson, Stefan, Jackson, Petra, and Vogel, Ulla

Subjects
TITANIUM dioxide nanoparticles, PULMONARY toxicology, GENETIC toxicology, BRONCHOALVEOLAR lavage, MESSENGER RNA, LABORATORY mice
Abstract

The influence of surface charge of nanomaterials on toxicological effects is not yet fully understood. We investigated the inflammatory response, the acute phase response and the genotoxic effect of two different titanium dioxide nanoparticles (TiO2 NPs) following a single intratracheal instillation. NRCWE-001 was unmodified rutile TiO2 with endogenous negative surface charge, whereas NRCWE-002 was surface modified to be positively charged. C57BL/6J BomTac mice received 18, 54 and 162 µg/mouse and were humanely killed 1, 3 and 28 days post-exposure. Vehicle controls were tested alongside for comparison. The cellular composition and protein concentration were determined in bronchoalveolar lavage (BAL) fluid as markers for an inflammatory response. Pulmonary and systemic genotoxicity was analysed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary and hepatic acute phase response was analysed by Saa3 mRNA levels in lung tissue or Saa1 mRNA levels in liver tissue by real-time quantitative polymerase chain reaction. Instillation of NRCWE-001 and -002 both induced a dosedependent neutrophil influx into the lung lining fluid and Saa3 mRNA levels in lung tissue at all assessed time points. There was no statistically significant difference between NRCWE-001 and NRCWE-002. Exposure to both TiO2 NPs induced increased levels of DNA strand breaks in lung tissue at all doses 1 and 28 days post-exposure and NRCWE-002 at the low and middle dose 3 days post-exposure. The DNA strand break levels were statistically significantly different for NRCWE-001 and -002 for liver and for BAL cells, but no consistent pattern was observed. In conclusion, functionalisation of reactive negatively charged rutile TiO2 to positively charged did not consistently influence pulmonary toxicity of the studied TiO2 NPs. [ABSTRACT FROM AUTHOR]

Published
2017
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28. Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity

Author

Poulsen, Sarah S., Jackson, Petra, Kling, Kirsten, Knudsen, Kristina B., Skaug, Vidar, Kyjovska, Zdenka O., Thomsen, Birthe L., Clausen, Per Axel, Rambabu Atluri, Berthing, Trine, Bengtson, Stefan, Wolff, Henrik, Jensen, Keld A., Wallin, Håkan, and Vogel, Ulla

Subjects
3. Good health
Abstract

Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial MWCNT (supplied in three groups of different dimensions, with one pristine and two/three surface modified in each group). We characterized morphology, chemical composition, surface area and functionalization levels. MWCNT were deposited in lungs of female C57BL/6J mice by intratracheal instillation of 0, 6, 18 or 54 μg/mouse. Pulmonary inflammation (neutrophil influx in bronchoalveolar lavage (BAL)) and genotoxicity were determined on day 1, 28 or 92. Histopathology of the lungs was performed on day 28 and 92. All MWCNT induced similar histological changes. Lymphocytic aggregates were detected for all MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length significantly predicted pulmonary inflammation, whereas surface oxidation (–OH and –COOH) was predictor of lowered inflammation on day 28. BET surface area, and therefore diameter, significantly predicted genotoxicity in BAL fluid cells and lung tissue such that lower BET surface area or correspondingly larger diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects.

30. Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity

Author

Poulsen, Sarah S., Jackson, Petra, Kling, Kirsten, Knudsen, Kristina B., Skaug, Vidar, Kyjovska, Zdenka O., Thomsen, Birthe L., Clausen, Per Axel, Rambabu Atluri, Berthing, Trine, Bengtson, Stefan, Wolff, Henrik, Jensen, Keld A., Wallin, Håkan, and Vogel, Ulla

Subjects
3. Good health
Abstract

Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial MWCNT (supplied in three groups of different dimensions, with one pristine and two/three surface modified in each group). We characterized morphology, chemical composition, surface area and functionalization levels. MWCNT were deposited in lungs of female C57BL/6J mice by intratracheal instillation of 0, 6, 18 or 54 μg/mouse. Pulmonary inflammation (neutrophil influx in bronchoalveolar lavage (BAL)) and genotoxicity were determined on day 1, 28 or 92. Histopathology of the lungs was performed on day 28 and 92. All MWCNT induced similar histological changes. Lymphocytic aggregates were detected for all MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length significantly predicted pulmonary inflammation, whereas surface oxidation (–OH and –COOH) was predictor of lowered inflammation on day 28. BET surface area, and therefore diameter, significantly predicted genotoxicity in BAL fluid cells and lung tissue such that lower BET surface area or correspondingly larger diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects.

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