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In Vitro Primary‐Indirect Genotoxicity in Bronchial Epithelial Cells Promoted by Industrially Relevant Few‐Layer Graphene
Author(s) -
Burgum Michael J.,
Clift Martin J. D.,
Evans Stephen J.,
Hondow Nicole,
Miller Mark,
Lopez Sandra Bustamante,
Williams Adam,
Tarat Afshin,
Jenkins Gareth J.,
Doak Shareen H.
Publication year - 2021
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.202002551
Subject(s) - genotoxicity , micronucleus test , chemistry , comet assay , oxidative stress , micronucleus , biophysics , population , cytotoxicity , surface modification , glutathione , dna damage , biochemistry , in vitro , toxicity , biology , organic chemistry , enzyme , dna , demography , sociology
Few‐layer graphene (FLG) has garnered much interest owing to applications in hydrogen storage and reinforced nanocomposites. Consequently, these engineered nanomaterials (ENMs) are in high demand, increasing occupational exposure. This investigation seeks to assess the inhalation hazard of industrially relevant FLG engineered with: (i) no surface functional groups (neutral), (ii) amine, and (iii) carboxyl group functionalization. A monoculture of human lung epithelial (16HBE14o ‐ ) cells is exposed to each material for 24‐h, followed by cytotoxicity and genotoxicity evaluation using relative population doubling (RPD) and the cytokinesis‐blocked micronucleus (CBMN) assay, respectively. Neutral‐FLG induces the greatest (two‐fold) significant increase ( p < 0.05) in micronuclei, whereas carboxyl‐FLG does not induce significant ( p < 0.05) genotoxicity. These findings correlate to significant ( p < 0.05) concentration‐dependent increases in interleukin (IL)‐8, depletion of intracellular glutathione (rGSH) and a depletion in mitochondrial ATP production. Uptake of FLG is evaluated by transmission electron microscopy, whereby FLG particles are observed within membrane‐bound vesicles in the form of large agglomerates (>1 µm diameter). The findings of the present study have demonstrated the capability of neutral‐FLG and amine‐FLG to induce genotoxicity in 16HBE14o ‐ cells through primary indirect mechanisms, suggesting a possible role for carboxyl groups in scavenging radicals produced via oxidative stress.