Genotoxic and inflammatory effects of nanofibrillated cellulose in murine lungs

Julia Catalán, Elina Rydman, Kukka Aimonen, Kati-Susanna Hannukainen, Satu Suhonen, Esa Vanhala, Carlos Moreno, Valérie Meyer, Denilson da Silva Perez, Asko Sneck, Ulla Forsström, Casper Højgaard, Martin Willemoes, Jacob R. Winther, Ulla Vogel, Henrik Wolff, Harri Alenius, Kai M. Savolainen, Hannu Norppa

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

Nanofibrillated cellulose (NFC) is a sustainable and renewable nanomaterial, with diverse potential applications in the paper and medical industries. As NFC consists of long fibres of high aspect ratio, we examined here whether TEMPO-(2,2,6,6-tetramethyl-piperidin-1-oxyl) oxidised NFC (length 300-1000 nm, thickness 10-25 nm), administrated by a single pharyngeal aspiration, could be genotoxic to mice, locally in the lungs or systemically in the bone marrow. Female C57Bl/6 mice were treated with four different doses of NFC (10, 40, 80 and 200 µg/mouse), and samples were collected 24 h later. DNA damage was assessed by the comet assay in bronchoalveolar lavage (BAL) and lung cells, and chromosome damage by the bone marrow erythrocyte micronucleus assay. Inflammation was evaluated by BAL cell counts and analysis of cytokines and histopathological alterations in the lungs. A significant induction of DNA damage was observed at the two lower doses of NFC in lung cells, whereas no increase was seen in BAL cells. No effect was detected in the bone marrow micronucleus assay, either. NFC increased the recruitment of inflammatory cells to the lungs, together with a dose-dependent increase in mRNA expression of tumour necrosis factor α, interleukins 1β and 6, and chemokine (C-X-C motif) ligand 5, although there was no effect on the levels of the respective proteins. The histological analysis showed a dose-related accumulation of NFC in the bronchi, the alveoli and some in the cytoplasm of macrophages. In addition, neutrophilic accumulation in the alveolar lung space was observed with increasing dose. Our findings showed that NFC administered by pharyngeal aspiration caused an acute inflammatory response and DNA damage in the lungs, but no systemic genotoxic effect in the bone marrow. The present experimental design did not, however, allow us to determine whether the responses were transient or could persist for a longer time.
Original languageEnglish
Pages (from-to)23-31
Number of pages9
JournalMutagenesis
Volume32
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017
MoE publication typeA1 Journal article-refereed

Fingerprint

Cellulose
Lung
Bone
Bronchoalveolar Lavage
Bone Marrow
DNA Damage
Assays
Micronucleus Tests
DNA
oxidized cellulose
CXC Chemokines
Comet Assay
Nanostructures
Macrophages
Bronchi
Chromosomes
Interleukin-1
Nanostructured materials
Transient analysis
Design of experiments

Keywords

  • safety
  • nanocellulose
  • NFC
  • nanofibrillated cellulose
  • cellulose nanofibrils
  • genotoxicity
  • inflammation
  • lungs
  • mice
  • occupational safety
  • DNA damage

Cite this

Catalán, J., Rydman, E., Aimonen, K., Hannukainen, K-S., Suhonen, S., Vanhala, E., ... Norppa, H. (2017). Genotoxic and inflammatory effects of nanofibrillated cellulose in murine lungs. Mutagenesis, 32(1), 23-31. https://doi.org/10.1093/mutage/gew035
Catalán, Julia ; Rydman, Elina ; Aimonen, Kukka ; Hannukainen, Kati-Susanna ; Suhonen, Satu ; Vanhala, Esa ; Moreno, Carlos ; Meyer, Valérie ; da Silva Perez, Denilson ; Sneck, Asko ; Forsström, Ulla ; Højgaard, Casper ; Willemoes, Martin ; Winther, Jacob R. ; Vogel, Ulla ; Wolff, Henrik ; Alenius, Harri ; Savolainen, Kai M. ; Norppa, Hannu. / Genotoxic and inflammatory effects of nanofibrillated cellulose in murine lungs. In: Mutagenesis. 2017 ; Vol. 32, No. 1. pp. 23-31.
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abstract = "Nanofibrillated cellulose (NFC) is a sustainable and renewable nanomaterial, with diverse potential applications in the paper and medical industries. As NFC consists of long fibres of high aspect ratio, we examined here whether TEMPO-(2,2,6,6-tetramethyl-piperidin-1-oxyl) oxidised NFC (length 300-1000 nm, thickness 10-25 nm), administrated by a single pharyngeal aspiration, could be genotoxic to mice, locally in the lungs or systemically in the bone marrow. Female C57Bl/6 mice were treated with four different doses of NFC (10, 40, 80 and 200 µg/mouse), and samples were collected 24 h later. DNA damage was assessed by the comet assay in bronchoalveolar lavage (BAL) and lung cells, and chromosome damage by the bone marrow erythrocyte micronucleus assay. Inflammation was evaluated by BAL cell counts and analysis of cytokines and histopathological alterations in the lungs. A significant induction of DNA damage was observed at the two lower doses of NFC in lung cells, whereas no increase was seen in BAL cells. No effect was detected in the bone marrow micronucleus assay, either. NFC increased the recruitment of inflammatory cells to the lungs, together with a dose-dependent increase in mRNA expression of tumour necrosis factor α, interleukins 1β and 6, and chemokine (C-X-C motif) ligand 5, although there was no effect on the levels of the respective proteins. The histological analysis showed a dose-related accumulation of NFC in the bronchi, the alveoli and some in the cytoplasm of macrophages. In addition, neutrophilic accumulation in the alveolar lung space was observed with increasing dose. Our findings showed that NFC administered by pharyngeal aspiration caused an acute inflammatory response and DNA damage in the lungs, but no systemic genotoxic effect in the bone marrow. The present experimental design did not, however, allow us to determine whether the responses were transient or could persist for a longer time.",
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Catalán, J, Rydman, E, Aimonen, K, Hannukainen, K-S, Suhonen, S, Vanhala, E, Moreno, C, Meyer, V, da Silva Perez, D, Sneck, A, Forsström, U, Højgaard, C, Willemoes, M, Winther, JR, Vogel, U, Wolff, H, Alenius, H, Savolainen, KM & Norppa, H 2017, 'Genotoxic and inflammatory effects of nanofibrillated cellulose in murine lungs', Mutagenesis, vol. 32, no. 1, pp. 23-31. https://doi.org/10.1093/mutage/gew035

Genotoxic and inflammatory effects of nanofibrillated cellulose in murine lungs. / Catalán, Julia; Rydman, Elina; Aimonen, Kukka; Hannukainen, Kati-Susanna; Suhonen, Satu; Vanhala, Esa; Moreno, Carlos; Meyer, Valérie; da Silva Perez, Denilson; Sneck, Asko; Forsström, Ulla; Højgaard, Casper; Willemoes, Martin; Winther, Jacob R.; Vogel, Ulla; Wolff, Henrik; Alenius, Harri; Savolainen, Kai M.; Norppa, Hannu.

In: Mutagenesis, Vol. 32, No. 1, 01.01.2017, p. 23-31.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Genotoxic and inflammatory effects of nanofibrillated cellulose in murine lungs

AU - Catalán, Julia

AU - Rydman, Elina

AU - Aimonen, Kukka

AU - Hannukainen, Kati-Susanna

AU - Suhonen, Satu

AU - Vanhala, Esa

AU - Moreno, Carlos

AU - Meyer, Valérie

AU - da Silva Perez, Denilson

AU - Sneck, Asko

AU - Forsström, Ulla

AU - Højgaard, Casper

AU - Willemoes, Martin

AU - Winther, Jacob R.

AU - Vogel, Ulla

AU - Wolff, Henrik

AU - Alenius, Harri

AU - Savolainen, Kai M.

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N2 - Nanofibrillated cellulose (NFC) is a sustainable and renewable nanomaterial, with diverse potential applications in the paper and medical industries. As NFC consists of long fibres of high aspect ratio, we examined here whether TEMPO-(2,2,6,6-tetramethyl-piperidin-1-oxyl) oxidised NFC (length 300-1000 nm, thickness 10-25 nm), administrated by a single pharyngeal aspiration, could be genotoxic to mice, locally in the lungs or systemically in the bone marrow. Female C57Bl/6 mice were treated with four different doses of NFC (10, 40, 80 and 200 µg/mouse), and samples were collected 24 h later. DNA damage was assessed by the comet assay in bronchoalveolar lavage (BAL) and lung cells, and chromosome damage by the bone marrow erythrocyte micronucleus assay. Inflammation was evaluated by BAL cell counts and analysis of cytokines and histopathological alterations in the lungs. A significant induction of DNA damage was observed at the two lower doses of NFC in lung cells, whereas no increase was seen in BAL cells. No effect was detected in the bone marrow micronucleus assay, either. NFC increased the recruitment of inflammatory cells to the lungs, together with a dose-dependent increase in mRNA expression of tumour necrosis factor α, interleukins 1β and 6, and chemokine (C-X-C motif) ligand 5, although there was no effect on the levels of the respective proteins. The histological analysis showed a dose-related accumulation of NFC in the bronchi, the alveoli and some in the cytoplasm of macrophages. In addition, neutrophilic accumulation in the alveolar lung space was observed with increasing dose. Our findings showed that NFC administered by pharyngeal aspiration caused an acute inflammatory response and DNA damage in the lungs, but no systemic genotoxic effect in the bone marrow. The present experimental design did not, however, allow us to determine whether the responses were transient or could persist for a longer time.

AB - Nanofibrillated cellulose (NFC) is a sustainable and renewable nanomaterial, with diverse potential applications in the paper and medical industries. As NFC consists of long fibres of high aspect ratio, we examined here whether TEMPO-(2,2,6,6-tetramethyl-piperidin-1-oxyl) oxidised NFC (length 300-1000 nm, thickness 10-25 nm), administrated by a single pharyngeal aspiration, could be genotoxic to mice, locally in the lungs or systemically in the bone marrow. Female C57Bl/6 mice were treated with four different doses of NFC (10, 40, 80 and 200 µg/mouse), and samples were collected 24 h later. DNA damage was assessed by the comet assay in bronchoalveolar lavage (BAL) and lung cells, and chromosome damage by the bone marrow erythrocyte micronucleus assay. Inflammation was evaluated by BAL cell counts and analysis of cytokines and histopathological alterations in the lungs. A significant induction of DNA damage was observed at the two lower doses of NFC in lung cells, whereas no increase was seen in BAL cells. No effect was detected in the bone marrow micronucleus assay, either. NFC increased the recruitment of inflammatory cells to the lungs, together with a dose-dependent increase in mRNA expression of tumour necrosis factor α, interleukins 1β and 6, and chemokine (C-X-C motif) ligand 5, although there was no effect on the levels of the respective proteins. The histological analysis showed a dose-related accumulation of NFC in the bronchi, the alveoli and some in the cytoplasm of macrophages. In addition, neutrophilic accumulation in the alveolar lung space was observed with increasing dose. Our findings showed that NFC administered by pharyngeal aspiration caused an acute inflammatory response and DNA damage in the lungs, but no systemic genotoxic effect in the bone marrow. The present experimental design did not, however, allow us to determine whether the responses were transient or could persist for a longer time.

KW - safety

KW - nanocellulose

KW - NFC

KW - nanofibrillated cellulose

KW - cellulose nanofibrils

KW - genotoxicity

KW - inflammation

KW - lungs

KW - mice

KW - occupational safety

KW - DNA damage

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Catalán J, Rydman E, Aimonen K, Hannukainen K-S, Suhonen S, Vanhala E et al. Genotoxic and inflammatory effects of nanofibrillated cellulose in murine lungs. Mutagenesis. 2017 Jan 1;32(1):23-31. https://doi.org/10.1093/mutage/gew035