title: Differential effects of metal ions on TCDD-induced cytotoxicity and cytochrome P4501A1 gene expression in a zebrafish liver (ZFL) cell-line.
abstract: Trace metal ions and trace organic compounds are common co-contaminants in the environment that pose risks to human health. We evaluated the effects of four metal ions (As(3+), Cu(2+), Hg(2+), and Zn(2+)) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced cytotoxicity and the expression of the cytochrome P4501A1 gene (cyp1a1) in the zebrafish liver (ZFL) cell line. A metal accumulation study showed that Cu and Zn did not accumulate in ZFL cells. However, As and Hg did accumulate, which resulted in the inhibition of TCDD-mediated induction of cyp1a1 mRNA and protein expression, and 7-ethoxyresorufin O-deethylase activity. A luciferase assay showed that both As(3+) and Hg(2+) inhibited the TCDD-induced activity of gene constructs containing either synthetic 3XRE or a distal cyp1a1 promoter region, implying that the decreased levels of TCDD-induced cyp1a1 were due to transcriptional effects. A proteomic study showed that the toxic effects of As(3+) might be due to changes in cellular metabolic processes, the cellular stimulation response and the cellular redox state in ZFL cells.
authors.affiliation: School of Life Sciences, Chinese University, Sha Tin, Hong Kong SAR, China. kingchan@cuhk.edu.hk.
authors.forename: Ying Ying
authors.initials: YY
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Chinese University, Sha Tin, Hong Kong SAR, China. kingchan@cuhk.edu.hk.
authors.forename: King Ming
authors.initials: KM
authors.lastname: Chan
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000032:analysis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D019216:Metals, Heavy / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D060066:Protein Interaction Maps / Q000187:drug effects; D040901:Proteomics; D015027:Zebrafish
chemical_list: D019216:Metals, Heavy; D000072317:Polychlorinated Dibenzodioxins; D019363:Cytochrome P-450 CYP1A1