TY - JOUR
T1 - Tungsten carbide-cobalt particles activate nrf2 and its downstream target genes in JB6 cells possibly by ROS generation
AU - Zhang, Xing Dong
AU - Zhao, Jinshun
AU - Bowman, Linda
AU - Shi, Xianglin
AU - Castranova, Vincent
AU - Ding, Min
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - Cancer; nanoparticles
KW - Nuclear factor erythroid 2-related factor 2 (Nrf2)
KW - Reactive oxygen species (ROS)
KW - Tungsten carbide-cobalt (WC-Co)
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U2 - 10.1615/JEnvironPatholToxicolOncol.v29.i1.60
DO - 10.1615/JEnvironPatholToxicolOncol.v29.i1.60
M3 - Article
C2 - 20528745
AN - SCOPUS:77952221619
SN - 0731-8898
VL - 29
SP - 31
EP - 40
JO - Journal of Environmental Pathology, Toxicology and Oncology
JF - Journal of Environmental Pathology, Toxicology and Oncology
IS - 1
ER -