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Tungsten carbide-cobalt particles activate Nrf2 and its downstream target genes in JB6 cells possibly by ROS generation.

Zhang-X-D; Zhao-J; Bowman-L; Shi-X; Castranova-V; Ding-M

J Environ Pathol Toxicol Oncol 2010 Jan; 29(1):31-40

http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.v29.i1.60

20036699

Hard metal consisting of a mixture of tungsten carbide (WC) and metallic cobalt (Co) was evaluated as a possible carcinogen in humans by IARC in 2003. Studies have suggested that nuclear factor erythroid 2-related factor 2 (Nrf2) constitutes one of the chemical-sensing and transcription systems that play an essential role(s) in chemical toxicity, carcinogenesis, and pathological processes. To elucidate the mechanisms of health hazards of WC-Co, effects of nano-WC-Co particles on Nrf2 signaling pathway were investigated in the present study in a JB6 cell line. After a 5 h treatment with nano-WC-Co particles, Nrf2 was released from Keap1 in the cytoplasm and translocated into the nucleus. Enzymatic activities of Nrf2 target genes, including glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), increased at 24 and 48 h after the treatment. Studies using reactive oxygen species (ROS) sensitive dyes indicated that ROS were produced in nano-WC-Co particle-treated cells. Pretreatment of the cells with catalase, but not sodium formate, resulted in a signifi cant inhibitory effect on nano-WC-Co particle-induced Nrf2 target gene activation. These fi ndings suggest that activation of Nrf2 and its downstream genes may be initiated by ROS generation, and ROS may act as a major contributor in nano-WC-Co particle-induced adverse health effects.

Tungsten-compounds; Nanotechnology; Cancer; Carcinogens; Carcinogenesis; Metals; Antioxidants; Mutagens; Mutation; Author Keywords: tungsten carbide-cobalt (WC-Co); cancer; nanoparticles; reactive oxygen species; ROS; nuclear factor erythroid 2-related factor 2; Nrf2

Min Ding, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505

JEPOEC

11130-73-7; 7440-48-4

20100101

Journal Article

mid5@cdc.gov

2010

1

0731-8898

HELD

Journal of Environmental Pathology, Toxicology, and Oncology

WV; KY