Low concentrations of 4-ABP promote liver carcinogenesis in human liver cells and a zebrafish model

Heng Dao Lin, Yi Kuan Tseng, Chiou Hwa Yuh, Ssu Ching Chen

研究成果: 雜誌貢獻期刊論文同行評審

摘要

4-Aminobiphenyl (4-ABP) is a human bladder cancer carcinogen found in the manufacture of azo dyes and the composition of cigarette smoke in the environment. To determine whether low concentrations of 4-ABP induced or promote liver carcinogenesis and investigate the underlying mechanism, we have established the liver cell carcinogenesis model in human liver cell lines and zebrafish to evaluate liver cancer development associated with long-term exposure to low concentrations of 4-ABP. Results show that repeated 4-ABP exposure promoted cellular proliferation and migration via the involvement of ROS in Ras/MEK/ERK pathway in vitro. Also, 4-ABP (1, 10, and 100 nM) induces hepatocellular carcinoma (HCC) formation in HBx, Src (p53-/-) transgenic zebrafish at four months of age and in wild-type zebrafish at seven months of age. In addition, we observed a correlation between the Ras-ERK pathway and 4-ABP-induced HCC in vitro and in vivo. Our finding suggests low concentrations of 4-ABP repeated exposure is a potential risk factor for liver cancer. To our knowledge, this is the first report on the promotion of liver carcinogenesis in human liver cells and zebrafish following 4-ABP exposure.

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文章編號126954
期刊Journal of Hazardous Materials
423
DOIs
出版狀態已出版 - 5 2月 2022

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