Differential effects of metal ions on TCDD-induced cytotoxicity and cytochrome P4501A1 gene expression in a zebrafish liver (ZFL) cell-linet

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 (As3+, Cu2+, Hg2+, and Zn2+) on 2,3,7,8-tetrachLorodibenzo-p-dioxin (TCDD) induced cytotoxicity and the expression of the cytochrome P4501A1 gene (cyplal) 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 cyplal mRNA and protein expression, and 7-ethoxyresorufin 0-deethyLase activity. A Luciferase assay showed that both As3+ and Hg2+ inhibited the TCDD-induced activity of gene constructs containing either synthetic 3XRE or a distal cyplal promoter region, implying that the decreased levels of TCDD-induced cyplal were due to transcriptional effects. A proteomic study showed that the toxic effects of As3+ might be due to changes in ceLLuLar metabolic processes, the ceLLuLar stimulation response and the ceLLuLar redox state in ZFL cells.