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 seq. 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 shows 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.

Tungsten exposure causes a selective loss of histone demethylase protein

“…Based on the evidence provided in this study and our previous investigations, 14 tungsten exposure should be a significant concern for human health despite its low cellular toxicity. Moreover, these findings should generate concern among regulatory agencies and industry to more seriously consider tungsten as a carcinogen.…”

“…Therefore, occupational exposures to tungsten raise significant toxicity concerns. Previously, we reported on tungsten's ability to induce cancer‐related endpoints including cell transformation, increased migration, xenograft growth in nude mice, and the activation of multiple cancer‐related pathways, following in vitro exposure to BEAS‐2B cells . Histone modifications have been identified following exposure to a number of other carcinogenic metals .…”

“…Previously, we reported on tungsten's ability to induce cancer-related endpoints including cell transformation, increased migration, xenograft growth in nude mice, and the activation of multiple cancer-related pathways, following in vitro exposure to BEAS-2B cells. 14 The cells were maintained in 10 cm 2 polystyrene tissue culture dishes in an incubator at 37°C with 5% CO 2 . Media were changed every 4 days as well as passaged using 0.05% trypsin-EDTA (GIBCO) as described previously.…”

Influence of Increasing Tungsten Concentrations and Soil Characteristics on Plant Uptake: Greenhouse Experiments with Zea mays

“…However, several ecotoxicological studies have discovered that under certain environmental conditions, tungsten compounds can be solubilized and enter the biogeochemical cycles [7,8]. Occupational studies on workers' exposure in industry where tungsten is used have revealed several adverse health effects [9].…”

High-resolution measurement and mapping of tungstate in waters, soils and sediments using the low-disturbance DGT sampling technique

“…Tungsten (W) is a metal toxin with suspected carcinogenic properties [1][2][3][4]. As a dense lithophilic element noted for its hardness, superior electrical conductivity, high melting point and corrosion-resistance, W has a wide range of uses in daily household items (such as lamp filaments), building and construction tools (i.e.…”