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Journal of Environmental Pathology, Toxicology and Oncology
IF: 1.625 5-Year IF: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v29.i1.60
pages 31-40

Tungsten Carbide-Cobalt Particles Activate Nrf2 and Its Downstream Target Genes in JB6 Cells Possibly by ROS Generation

Xing-Dong Zhang
Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40515; Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
Jinshun Zhao
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505
Linda Bowman
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
Xianglin Shi
Division of Nutritional Sciences, Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY; Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY; Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY
Vincent Castranova
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505
Min Ding
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505

ABSTRACT

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.


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