Size-dependent effects of tungsten carbide-cobalt particles on induction of oxidative stress and activation of cell signaling pathways in vitro.
Shvedova-AA; Kisin-ER; Murray-AR; Zhao-J; Bowman-L; Lu-Y; Jiang-B; Leonard-SS; Vallyathan-V; Castranova-V; Fadeel-B; Ding-M
Toxicologist 2010 Mar; 114(1):59
Hard metal or cemented carbide consists of a mixture of tungsten carbide (WC) (85%) and metallic cobalt (Co) (5-15%). WC-Co is considered to be potentially carcinogenic to humans. However, no comparison of the adverse effects of nanosized WC-Co particles is available to date. In the present study, we compared the ability of nano- and fine-sized WC-Co particles to form free radicals, and propensity to activate the transcription factors, AP-1 and NF-êB, along with stimulation of mitogen-activated protein kinase (MAPK) signaling pathways in a mouse epidermal cell line (JB6 P+). Our results demonstrated that nano-WC-Co generated a higher level of hydroxyl radicals, induced greater oxidative stress, as evidenced by a decrease of GSH levels, and caused faster JB6 P+ cell growth/proliferation than observed after exposure of cells to fine-WC-Co. In addition, nano-WC-Co activated AP-1 and NF-kappaB more efficiently in JB6 P+ cells, as compared to fine-WC-Co. Experiments using AP-1-luciferase reporter transgenic mice confirmed the activation of AP-1 by nano-WC-Co. Nano- and fine-sized WC-Co particles also stimulated MAPKs, including ERKs, p38, and JNKs with significantly higher potency of nano-WC-Co. Overall, these findings demonstrated that both fine- and nano-sized WC-Co induce ROS generation, cell proliferation, and activation of specific cell signaling pathways. These studies also underscore that size is a critical factor in assessment of toxicological and biological responses of WC-Co materials
Biological-effects; Cell-biology; Cellular-reactions; Chemical-hypersensitivity; Chemical-properties; Exposure-assessment; Exposure-levels; Exposure-methods; Laboratory-animals; Laboratory-testing; Microbiology; Microscopic-analysis; Molecular-biology; Oxidation; Oxidative-metabolism; Oxides; Particulate-dust; Particulates; Toxic-effects; Toxic-materials
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah
University of Pittsburgh at Pittsburgh