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Title: Tungsten-induced carcinogenesis in human bronchial epithelial cells

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. - Highlights: • Tungsten (W) induces cell transformation and increases migration in vitro. • W increases xenograftmore » growth in nude mice. • W altered the expression of cancer-related genes such as those involved in leukemia. • Some of the dysregulated leukemia genes include, CD74, CTGF, MST4, and HOXB5. • For the first time, data is presented that demonstrates tungsten's carcinogenic potential.« less

Authors:
; ; ; ; ; ;  [1];  [2];  [3]; ; ;  [4];  [1]
  1. Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987 (United States)
  2. Genome Technology Center, New York University Langone Medical Center, New York, NY 10016 (United States)
  3. Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, NY 10016 (United States)
  4. Department of Chemistry and Pharmacy, University of Sassari, Sassari (Italy)
Publication Date:
OSTI Identifier:
22687764
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 288; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AGAR; ARSENIC; BERYLLIUM; CADMIUM; CARCINOGENESIS; CARCINOGENS; CELL TRANSFORMATIONS; GENES; LEUKEMIA; LUNGS; MICE; NICKEL; RNA; TUNGSTEN

Citation Formats

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, and Costa, Max, E-mail: Max.Costa@nyumc.org. Tungsten-induced carcinogenesis in human bronchial epithelial cells. United States: N. p., 2015. Web. doi:10.1016/J.TAAP.2015.07.003.
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, E-mail: Max.Costa@nyumc.org. Tungsten-induced carcinogenesis in human bronchial epithelial cells. United States. doi:10.1016/J.TAAP.2015.07.003.
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, and Costa, Max, E-mail: Max.Costa@nyumc.org. Thu . "Tungsten-induced carcinogenesis in human bronchial epithelial cells". United States. doi:10.1016/J.TAAP.2015.07.003.
@article{osti_22687764,
title = {Tungsten-induced carcinogenesis in human bronchial epithelial cells},
author = {Laulicht, Freda and Brocato, Jason and Cartularo, Laura and Vaughan, Joshua and Wu, Feng and Kluz, Thomas and Sun, Hong and Oksuz, Betul Akgol and Shen, Steven and Peana, Massimiliano and Medici, Serenella and Zoroddu, Maria Antonietta and Costa, Max, E-mail: Max.Costa@nyumc.org},
abstractNote = {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. - Highlights: • Tungsten (W) induces cell transformation and increases migration in vitro. • W increases xenograft growth in nude mice. • W altered the expression of cancer-related genes such as those involved in leukemia. • Some of the dysregulated leukemia genes include, CD74, CTGF, MST4, and HOXB5. • For the first time, data is presented that demonstrates tungsten's carcinogenic potential.},
doi = {10.1016/J.TAAP.2015.07.003},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 288,
place = {United States},
year = {2015},
month = {10}
}