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
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
Journal of Environmental Pathology, Toxicology, and Oncology