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Impact of nanocelluloses on genome-wide DNA methylation pattern of human pulmonary and intestinal cells
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Resumo(s)
Objective: Nanocellulose is an innovative nanomaterial with interesting physicochemical properties for several industrial and biomedical applications and its safety for human health must be ensured. This study aimed to identify DNA methylation changes in human pulmonary and intestinal cells after exposure to two fibrillar celluloses with different physicochemical properties, both derived from Eucaliptus globulus. Their cellular effects were investigated in silico by functional pathway and gene ontology (GO) analysis.
Methods: We applied Reduced Representation Bisulfite Sequencing to analyze the methylation differences in DNA CpG-rich regions from human bronchial (BEAS-2B) and intestinal (Caco-2) cells exposed for 24h to 14.3 µg/mL of cellulose nanofibrils (CNF) or microfibrils (CMF) versus non-exposed ones. A bioinformatics pipeline was implemented for identifying differentially methylated genes (DMGs), functional pathways, and GO associations.
Results: CNF and CMF exposure resulted in 11 and 14 DMGs, respectively, in BEAS-2B cells, 6 being common to both nanocelluloses. In Caco-2 cells, 36 and 31 DMGs were identified, sharing 12 DMGs. No DMGs were shared between these cell lines. Hypomethylation predominated in BEAS-2B cells, and hypermethylation in Caco-2 cells. In BEAS-2B cells, both nanocelluloses affected similar pathways and GO terms (e.g., regulation of DNA replication, damage repair and senescence, telomere maintenance, and D-glucose transport). In Caco-2 cells, both CNF and CMF enriched, for instance, signal transduction, glycosylation, and cytoskeletal dynamics. Each nanocellulose type also affected other different pathways and terms.
Conclusions: Nanocellulose may have a wide impact on the metabolism and survival of pulmonary and intestinal cells through several regulatory pathways, which depend on nanocellulose physicochemical properties. Cell type also influences the outcome, suggesting tissue-specific effects. These findings highlight the relevance of DNA methylation in nanotoxicology, providing insights into underlying molecular mechanisms of action.
Keywords: gene ontology; nanomaterial; pathway analysis; RRBS
Descrição
Palavras-chave
DNA Methylation Nanocellulose PARC Environmental Genotoxicity Genotoxicidade Ambiental