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A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals
Published on: June 25, 2018
Exposure to oxygenated polycyclic aromatic hydrocarbons and endocrine dysfunction: Multi-level study based on hormone
Ying Ren1, Yue Wang2, Yang Wang1
1Shanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, PR China.
Oxygenated polycyclic aromatic hydrocarbons (OPAHs) can disrupt endocrine systems. This study found that 1,2-benzanthraquinone (BAQ) shows strong hormonal activity and causes developmental toxicity in zebrafish larvae.
Area of Science:
- Environmental Science
- Toxicology
- Endocrinology
Background:
- Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are emerging contaminants with high toxicity.
- OPAHs' endocrine-disrupting potential is debated, with controversial reports.
- Understanding OPAHs' interaction with hormone receptors is crucial for risk assessment.
Purpose of the Study:
- To investigate the endocrine-disrupting effects of typical OPAHs.
- To identify specific OPAHs with significant hormonal activity.
- To elucidate the mechanisms of OPAH-receptor interactions and their developmental toxicity.
Main Methods:
- Dual luciferase reporter gene assay and molecular docking to assess OPAH-hormone receptor interactions.
- Development of a weighted scoring system for OPAH hormonal effect screening.
- In vivo zebrafish larvae exposure model to evaluate developmental toxicity.
- Construction of androgen response element-enhanced green fluorescent protein (ARE-EGFP) zebrafish embryos.
Main Results:
- Five typical OPAHs showed agonistic activity towards hormone receptors (ERα/AR/GRα/TRβ).
- Hydrogen bonding and hydrophobic interactions mediate OPAH-receptor binding.
- 1,2-benzanthraquinone (BAQ) exhibited the strongest hormonal effects, while anthraquinone (AQ) showed the weakest.
- BAQ induced developmental toxicity in zebrafish, including altered androgen receptor expression and key hormone synthesis genes, pericardial edema, and reduced body length.
- BAQ demonstrated androgenic potency in ARE-EGFP zebrafish embryos, unlike AQ.
Conclusions:
- OPAHs, particularly BAQ, possess significant endocrine-disrupting capabilities.
- BAQ's hormonal activity is linked to developmental toxicity in aquatic organisms.
- These findings underscore the importance of considering OPAHs' endocrine-disrupting effects in environmental risk management.
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