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Titanium dioxide nanofibers induce angiogenic markers and genomic instability in lung cells leading to a highly dedifferentiated and fibrotic tumor formation in a xenograft model

Abstract

The synthesis of novel nanofibers has increased due to its broad spectrum of applications which have raised also the concern of toxicity mediated by inhalation. Titanium dioxide (TiO2), classified as a possible carcinogen to humans by the International Agency for Research on Cancer regardless of size and shape, is being manufactured as nanofibers for water waste cleaning, enhanced miRNAs extraction, glucose quantification and others devices. Toxicological studies of TiO2 nanofibers have shown the capability to induce sustained inflammation, frustrated phagocytosis, and lysosomal disruption but the capability to acquire or enhance aggressive characteristics, including angiogenesis, fibrosis or epithelial mesenchymal transition (EMT) and has not been investigated. In this study, we synthetized TiO2 nanofibers (anatase phase; 61.5±4.9 nm width and 3.1±0.2 µm length) to expose monolayers of lung epithelial cells (1 and 10 µg/cm2) for 7 days and angiogenesis, fibrosis, EMT markers, genomic instability and cisplatin sensibility were measured. Then, those cells were harvested and injected subcutaneously in a xenograft mice model for tumor development. After 11 weeks, the same markers were measured in the tumors. Monolayers exposed to TiO2 nanofibers induced angiogenic, fibrotic and EMT markers, genomic instability and loss of cisplatin sensibility. Tumors developed from exposed cells to TiO2 nanofibers were also positive for the same markers and moreover, dedifferentiation, remarkable presence of erythrocytes and higher loss of cisplatin sensibility were higher, which suggests that TiO2 nanofibers enhance aggressive tumor phenotype in lung epithelial cells.

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Publication details

The article was received on 25 Sep 2018, accepted on 26 Nov 2018 and first published on 26 Nov 2018


Article type: Paper
DOI: 10.1039/C8EN01078A
Citation: Environ. Sci.: Nano, 2018, Accepted Manuscript
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    Titanium dioxide nanofibers induce angiogenic markers and genomic instability in lung cells leading to a highly dedifferentiated and fibrotic tumor formation in a xenograft model

    E. I. Medina-Reyes, N. L. Delgado-Buenrostro, A. Déciga-Alcaraz, V. Freyre-Fonseca, J. O. Flores-Flores, R. Hernández-Pando, J. Barrios-Payán , J. C. Carrero, Y. Sánchez-Pérez, C. M. García-Cuéllar, F. Vaca-Paniagua and Y. I. Chirino, Environ. Sci.: Nano, 2018, Accepted Manuscript , DOI: 10.1039/C8EN01078A

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