Literature DB >> 26164860

Tungsten-induced carcinogenesis in human bronchial epithelial cells.

Freda Laulicht1, Jason Brocato1, Laura Cartularo1, Joshua Vaughan1, Feng Wu1, Thomas Kluz1, Hong Sun1, Betul Akgol Oksuz2, Steven Shen3, Massimiliano Peana4, Serenella Medici4, Maria Antonietta Zoroddu4, Max Costa5.   

Abstract

Metals such as arsenic, cadmium, beryllium, and nickel are known human carcinogens; however, other transition metals, such as tungsten (W), remain relatively uninvestigated with regard to their potential carcinogenic activity. Tungsten production for industrial and military applications has almost doubled over the past decade and continues to increase. Here, for the first time, we demonstrate tungsten's ability to induce carcinogenic related endpoints including cell transformation, increased migration, xenograft growth in nude mice, and the activation of multiple cancer-related pathways in transformed clones as determined by RNA sequencing. Human bronchial epithelial cell line (Beas-2B) exposed to tungsten developed carcinogenic properties. In a soft agar assay, tungsten-treated cells formed more colonies than controls and the tungsten-transformed clones formed tumors in nude mice. RNA-sequencing data revealed that the tungsten-transformed clones altered the expression of many cancer-associated genes when compared to control clones. Genes involved in lung cancer, leukemia, and general cancer genes were deregulated by tungsten. Taken together, our data show the carcinogenic potential of tungsten. Further tests are needed, including in vivo and human studies, in order to validate tungsten as a carcinogen to humans.
Copyright © 2015 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Beas-2B; Cancer; In vitro; Nude mice; RNA-Seq; Tungsten

Mesh:

Substances:

Year:  2015        PMID: 26164860      PMCID: PMC4579035          DOI: 10.1016/j.taap.2015.07.003

Source DB:  PubMed          Journal:  Toxicol Appl Pharmacol        ISSN: 0041-008X            Impact factor:   4.219


  39 in total

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