PUBLICATION
Differential effects of metal ions on TCDD-induced cytotoxicity and cytochrome P4501A1 gene expression in a zebrafish liver (ZFL) cell-line
- Authors
- Chen, Y.Y., Chan, K.M.
- ID
- ZDB-PUB-151128-4
- Date
- 2016
- Source
- Metallomics : integrated biometal science 8(2): 236-51 (Journal)
- Registered Authors
- Chan, King-Ming
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line
- Cell Survival/drug effects
- Cytochrome P-450 CYP1A1/analysis
- Cytochrome P-450 CYP1A1/drug effects*
- Cytochrome P-450 CYP1A1/genetics
- Cytochrome P-450 CYP1A1/metabolism*
- Gene Expression/drug effects*
- Liver/drug effects*
- Liver/metabolism
- Metals, Heavy/toxicity*
- Polychlorinated Dibenzodioxins/toxicity*
- Protein Interaction Maps/drug effects
- Proteomics
- Zebrafish
- PubMed
- 26612010 Full text @ Metallomics
Citation
Chen, Y.Y., Chan, K.M. (2016) Differential effects of metal ions on TCDD-induced cytotoxicity and cytochrome P4501A1 gene expression in a zebrafish liver (ZFL) cell-line. Metallomics : integrated biometal science. 8(2):236-51.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping