Single-Walled vs. Multi-Walled Carbon Nanotubes: Influence of Physico-Chemical Properties on Toxicogenomics Responses in Mouse Lungs

Abstract

Single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) are nanomaterials with one or multiple layers of carbon sheets. While it is suggested that various properties influence their toxicity, the specific mechanisms are not completely known. This study was aimed to determine if single or multi-walled structures and surface functionalization influence pulmonary toxicity and to identify the underlying mechanisms of toxicity. Female C57BL/6J BomTac mice were exposed to a single dose of 6, 18, or 54 μg/mouse of twelve SWCNTs or MWCNTs of different properties. Neutrophil influx and DNA damage were assessed on days 1 and 28 post-exposure. Genome microarrays and various bioinformatics and statistical methods were used to identify the biological processes, pathways and functions altered post-exposure to CNTs. All CNTs were ranked for their potency to induce transcriptional perturbation using benchmark dose modelling. All CNTs induced tissue inflammation. MWCNTs were more genotoxic than SWCNTs. Transcriptomics analysis showed similar responses across CNTs at the pathway level at the high dose, which included the perturbation of inflammatory, cellular stress, metabolism, and DNA damage responses. Of all CNTs, one pristine SWCNT was found to be the most potent and potentially fibrogenic, so it should be prioritized for further toxicity testing.

Time-Course of Transcriptomic Change in the Lungs of F344 Rats Repeatedly Exposed to a Multiwalled Carbon Nanotube in a 2-Year Test

“…At Year 1, activation of some metabolic and biogenesis-related pathways was noted; however, activation of these pathways seems not to be specific to Year 1, but rather to be maintained until Year 2 (phospholipase and some nuclear receptor signaling pathways) ( Figure 10 ). Recently, impairment of pulmonary lipid homeostasis has been addressed in studies of the toxicities of electronic cigarettes and nanomaterials, including CNTs [ 22 , 52 , 53 , 54 , 55 ]. It was found that this could profoundly affect surfactant metabolism, lamellar body biogenesis in type II pneumocytes, and the plasticity and functions of alveolar macrophages.…”

“…At Year 2, several interesting canonical pathways were identified ( Figure 4 and Figure 10 ), many of which are not included in previous toxicogenomic reports analyzing CNTs ( Tables S8 and S9, and Figure S7 ) [ 16 , 17 , 18 , 22 , 24 , 38 , 39 , 40 , 41 , 42 ]. ERBB Signaling Pathway was significantly perturbed, but IPA analysis could not determine whether this pathway was upregulated or downregulated (z-score: −0.9).…”

“…The other limitation is that we analyzed only one type of MWCNT and used animals exposed to only one dosage level of this MWCNT. Previous toxicogenomic analyses for CNTs have clearly demonstrated dose-dependent results [ 16 , 38 ], and some comparative analyses have discovered some physicochemical feature-dependent gene expression patterns [ 22 , 23 ]. In particular, if we had prepared another negative control group (dosed with a “non-carcinogenic fiber”), it would have provided a better comparison.…”

“…Shvedova et al evaluated mRNA and ncRNA in the blood of workers in a CNT factory to search for potential biomarkers for monitoring MWCNT exposure in humans [ 21 ]. In addition, researchers applied this powerful tool for grouping and classifying various test materials [ 22 , 23 , 24 ]. Most of these omics readouts demonstrated that CNT exposure resulted in a similar pattern of enrichment of genes involved in pathways and networks associated with inflammation, reactive oxygen species (ROS) generation, fibrosis, DNA damage, and cell proliferation.…”

Stretchable and Self-Adhesive PEDOT:PSS/MXene Dry Electrode with Low Contact Impedance for ECG Monitoring

“…Therefore, the contact impedance on the skin is several orders of magnitude higher than that of Ag/AgCl gel electrodes, leading to a unsatisfactory SNR. There is also concern about the toxicity of the nanofillers [17][18][19] .…”