Tungsten-induced carcinogenesis in human bronchial epithelial cells

Freda Laulicht, Jason Brocato, Laura Cartularo, Joshua Vaughan, Feng Wu, Thomas Kluz, Hong Sun, Betul Akgol Oksuz, Steven Shen, Massimilano Paena, Serenella Medici, Maria Antonietta Zoroddu, Max Costa

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)33-39
Number of pages7
JournalToxicology and Applied Pharmacology
Volume288
Issue number1
DOIs
StatePublished - Oct 1 2015

Keywords

  • Beas-2B
  • Cancer
  • In vitro
  • Nude mice
  • RNA-Seq
  • Tungsten

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