Characterization of genotoxic response to 15 multiwalled carbon nanotubes with variable physicochemical properties including surface functionalizations in the FE1-Muta(TM) mouse lung epithelial cell line

TY - JOUR

T1 - Characterization of genotoxic response to 15 multiwalled carbon nanotubes with variable physicochemical properties including surface functionalizations in the FE1-Muta(TM) mouse lung epithelial cell line

AU - Jackson, Petra

AU - Kling, Kirsten

AU - Jensen, Keld Alstrup

AU - Clausen, Per Axel

AU - Madsen, Anne Mette

AU - Wallin, Håkan

AU - Vogel, Ulla

N1 - © 2014 Wiley Periodicals, Inc.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Carbon nanotubes vary greatly in physicochemical properties. We compared cytotoxic and genotoxic response to 15 multiwalled carbon nanotubes (MWCNT) with varying physicochemical properties to identify drivers of toxic responses. The studied MWCNT included OECD Working Party on Manufactured Nanomaterials (WPMN) (NM-401, NM-402, and NM-403), materials (NRCWE-026 and MWCNT-XNRI-7), and three sets of surface-modified MWCNT grouped by physical characteristics (thin, thick, and short I-III, respectively). Each Groups I-III included pristine, hydroxylated and carboxylated MWCNT. Group III also included an amino-functionalized MWCNT. The level of surface functionalization of the MWCNT was low. The level and type of elemental impurities of the MWCNT varied by <2% of the weight, with exceptions. Based on dynamic light scattering data, the MWCNT were well-dispersed in stock dispersion of nanopure water with 2% serum, but agglomerated and sedimented during exposure. FE1-Muta(TM) Mouse lung epithelial cells were exposed for 24 hr. The levels of DNA strand breaks (SB) were evaluated using the comet assay, a screening assay suitable for genotoxicity testing of nanomaterials. Exposure to MWCNT (12.5-200 μg/ml) did not induce significant cytotoxicity (viability above 92%). Cell proliferation was reduced in highest doses of some MWCNT after 24 hr, and was associated with generation of reactive oxygen species and high surface area. Increased levels of DNA SB were only observed for Group II consisting of MWCNT with large diameters and high Fe2O3 and Ni content. Significantly, increased levels of SB were only observed at 200 μg/ml of MWCNT-042. Overall, the MWCNT were not cytotoxic and weakly genotoxic after 24 hr exposure to doses up to 200 μg/ml.

AB - Carbon nanotubes vary greatly in physicochemical properties. We compared cytotoxic and genotoxic response to 15 multiwalled carbon nanotubes (MWCNT) with varying physicochemical properties to identify drivers of toxic responses. The studied MWCNT included OECD Working Party on Manufactured Nanomaterials (WPMN) (NM-401, NM-402, and NM-403), materials (NRCWE-026 and MWCNT-XNRI-7), and three sets of surface-modified MWCNT grouped by physical characteristics (thin, thick, and short I-III, respectively). Each Groups I-III included pristine, hydroxylated and carboxylated MWCNT. Group III also included an amino-functionalized MWCNT. The level of surface functionalization of the MWCNT was low. The level and type of elemental impurities of the MWCNT varied by <2% of the weight, with exceptions. Based on dynamic light scattering data, the MWCNT were well-dispersed in stock dispersion of nanopure water with 2% serum, but agglomerated and sedimented during exposure. FE1-Muta(TM) Mouse lung epithelial cells were exposed for 24 hr. The levels of DNA strand breaks (SB) were evaluated using the comet assay, a screening assay suitable for genotoxicity testing of nanomaterials. Exposure to MWCNT (12.5-200 μg/ml) did not induce significant cytotoxicity (viability above 92%). Cell proliferation was reduced in highest doses of some MWCNT after 24 hr, and was associated with generation of reactive oxygen species and high surface area. Increased levels of DNA SB were only observed for Group II consisting of MWCNT with large diameters and high Fe2O3 and Ni content. Significantly, increased levels of SB were only observed at 200 μg/ml of MWCNT-042. Overall, the MWCNT were not cytotoxic and weakly genotoxic after 24 hr exposure to doses up to 200 μg/ml.

KW - Animals

KW - Cell Line

KW - Cell Proliferation

KW - Cell Survival

KW - Comet Assay

KW - DNA Damage

KW - Epithelial Cells

KW - Lung

KW - Mice

KW - Mutagenicity Tests

KW - Mutagens

KW - Nanotubes, Carbon

KW - Reactive Oxygen Species

U2 - 10.1002/em.21922

DO - 10.1002/em.21922

M3 - Journal article

C2 - 25393212

SN - 0893-6692

VL - 56

SP - 183

EP - 203

JO - Environmental and Molecular Mutagenesis

JF - Environmental and Molecular Mutagenesis

IS - 2

ER -