PUBLICATION
AhR agonist activity confirmation of polyhalogenated carbazoles (PHCZs) using an integration of in vitro, in vivo, and in silico models
- Authors
- Ji, C., Shen, C., Zhou, Y., Zhu, K., Sun, Z., Zuo, Z., Zhao, M.
- ID
- ZDB-PUB-191119-2
- Date
- 2019
- Source
- Environmental science & technology 53(24): 14716-14723 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Carbazoles
- Dioxins*
- Molecular Docking Simulation
- Polychlorinated Dibenzodioxins*
- Receptors, Aryl Hydrocarbon
- Zebrafish
- PubMed
- 31738530 Full text @ Env. Sci. Tech.
Citation
Ji, C., Shen, C., Zhou, Y., Zhu, K., Sun, Z., Zuo, Z., Zhao, M. (2019) AhR agonist activity confirmation of polyhalogenated carbazoles (PHCZs) using an integration of in vitro, in vivo, and in silico models. Environmental science & technology. 53(24):14716-14723.
Abstract
Polyhalogenated carbazoles (PHCZs) are a kind of rising environmental pollutants that have been reported to pose high risk to human beings and natural environment. PHCZs are of a similar molecular structure with of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and exhibited some dioxin-like toxicity. Dioxin-like compounds (DLCs) are required to be banned by the Stockholm Convention due to their potential adverse impacts to the environment and public health. However, few efforts have been done towards the regulation of PHCZs. Herein, we initiated multi-models to systematically determine and validate the dioxin-like effects of PHCZs in a large scale. Transgenic zebrafish line-Tg(cyp1a-12DRE:EGFP) and stably transfected HepG2 cell line with luciferase reporter plasmids were used to screen and evaluate the aryl hydrocarbon receptor (AhR) agonist effects of the target PHCZs, which were then verified by application of molecular docking and expression levels of AhR downstream genes. Results of the two bioassays showed that most of the tested PHCZs could pose dioxin-like AhR agonist effects, change the expression levels of AhR downstream genes, and interact with AhR in accordance with TCDD. In summary, data presented here can help to guide the safe use and regulation of PHCZs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping