%0 Journal Article %A Zhang, Xing-Dong %A Zhao, Jinshun %A Bowman, Linda %A Shi, Xianglin %A Castranova, Vincent %A Ding, Min %D 2010 %I Begell House %K tungsten carbide-cobalt (WC-Co), cancer; nanoparticles, reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (Nrf2) %N 1 %P 31-40 %R 10.1615/JEnvironPatholToxicolOncol.v29.i1.60 %T Tungsten Carbide-Cobalt Particles Activate Nrf2 and Its Downstream Target Genes in JB6 Cells Possibly by ROS Generation %U https://www.dl.begellhouse.com/journals/0ff459a57a4c08d0,265fcbc773531109,6892a5bb2a25703c.html %V 29 %X 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 significant inhibitory effect on nano-WC-Co particle-induced Nrf2 target gene activation. These findings 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. %8 2010-04-23