Evaluating the genotoxicity of cellulose nanofibrils in a co-culture of human lung epithelial cells and monocyte-derived macrophages

• Published in: Toxicology letters 2018-07, Vol.291, p.173-183
• Main Authors: Ventura, Célia, Lourenço, Ana Filipa, Sousa-Uva, António, Ferreira, Paulo J.T., Silva, Maria João
• Format: Article
• Language: English
• Subjects: A549 Cells; Cell Survival - drug effects; Cell Transformation, Neoplastic - drug effects; Cellulose - toxicity; Cellulose nanofibrils; Coculture Techniques; Comet Assay; DNA Damage; Epithelial Cells - drug effects; Eucalyptus - chemistry; Humans; Immunotoxicity; Interleukin-1beta - drug effects; Interleukin-1beta - metabolism; Lung - cytology; Lung - drug effects; Macrophages - drug effects; Micronucleus assay; Micronucleus Tests; Monocytes - drug effects; Mutagenicity Tests; Mutagens - toxicity; Nanofibers - toxicity; Safety assessment
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2018.04.013

•Cellulose nanofibrils (CNF) produced from Eucalyptus globulus were characterized.•A co-culture of lung alveolar cells and macrophages was used to analyse CNF toxicity.•No secretion of proinflammatory cytokine IL-1β was detected in exposed co-cultures.•Low CNF concentrations induced lung alveolar cells overgrowth.•CNF was genotoxic at low, but not at high concentrations (micronucleus assay). Cellulose nanofibrils (CNF) are manufactured nanofibres that hold impressive expectations in forest, food, pharmaceutical, and biomedical industries. CNF production and applications are leading to an increased human exposure and thereby it is of utmost importance to assess its safety to health. In this study, we screened the cytotoxic, immunotoxic and genotoxic effects of a CNF produced by TEMPO-mediated oxidation of an industrial bleached Eucalyptus globulus kraft pulp on a co-culture of lung epithelial alveolar (A549) cells and monocyte-derived macrophages (THP-1 cells). The results indicated that low CNF concentrations can stimulate A549 cells proliferation, whereas higher concentrations are moderately toxic. Moreover, no proinflammatory cytokine IL-1β was detected in the co-culture medium suggesting no immunotoxicity. Although CNF treatment did not induce sizable levels of DNA damage in A549 cells, it leaded to micronuclei formation at 1.5 and 3 μg/cm2. These findings suggest that this type of CNF is genotoxic through aneugenic or clastogenic mechanisms. Noteworthy, cell overgrowth and genotoxicity, which are events relevant for cell malignant transformation, were observed at low CNF concentration levels, which are more realistic and relevant for human exposure, e.g., in occupational settings.