Title: Tungsten-induced carcinogenesis in human bronchial epithelial cells.
Authors: Laulicht, Freda; Brocato, Jason; Cartularo, Laura; Vaughan, Joshua; Wu, Feng; Kluz, Thomas; Sun, Hong; Oksuz, Betul Akgol; Shen, Steven; Peana, Massimiliano; Medici, Serenella; Zoroddu, Maria Antonietta; Costa, Max
Published In Toxicol Appl Pharmacol, (2015 Oct 01)
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.
PubMed ID: 26164860
MeSH Terms: Animals; Bronchi/drug effects*; Bronchi/metabolism; Bronchi/pathology; Cell Line; Cell Movement/drug effects; Cell Proliferation/drug effects; Cell Transformation, Neoplastic/chemically induced*; Cell Transformation, Neoplastic/genetics; Cell Transformation, Neoplastic/metabolism; Cell Transformation, Neoplastic/pathology; Epithelial Cells/drug effects*; Epithelial Cells/metabolism; Epithelial Cells/pathology; Female; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Lung Neoplasms/chemically induced*; Lung Neoplasms/genetics; Lung Neoplasms/metabolism; Lung Neoplasms/pathology; Mice, Nude; Neoplasm Transplantation; Time Factors; Tumor Burden/drug effects; Tungsten Compounds/toxicity*