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A high throughput screening assay for human Thyroperoxidase inhibitors
Hongyan Dong1, Katie Paul Friedman2, Alain Filiatreault1
1Hazard Identification Division, Environmental Health Science & Research Bureau, Health Canada, Ottawa, Ontario, Canada.
Summary
A new assay using human thyroid peroxidase (hTPO) effectively identifies moderate to strong chemical inhibitors, offering a more accurate, human-relevant alternative to rat-based methods for hazard assessment.
Area of Science:
- Toxicology
- Biochemistry
- Chemical Safety
Background:
- Developing rapid, human-relevant assays is crucial for assessing chemical hazards.
- Thyroid peroxidase (TPO) is a key target for endocrine disruption.
- Existing assays often use animal-derived enzymes, limiting human relevance.
Purpose of the Study:
- To evaluate a new Amplex Ultra Red assay for human TPO (AUR-hTPO) inhibition.
- To compare its performance against a rat TPO assay (AUR-rTPO).
- To assess the utility of AUR-hTPO for identifying chemical hazards.
Main Methods:
- Tested 788 chemicals from the US EPA ToxCast Inventory using a tiered approach.
- Utilized human TPO enzyme from engineered cell lines.
- Compared results with rat TPO assay data and literature evidence.
Main Results:
- The AUR-hTPO assay showed consistent results with reference chemicals.
- 190 chemicals inhibited hTPO, with 158 showing no non-specific activity.
- The human assay demonstrated a lower false positive rate than the rat assay.
Conclusions:
- The AUR-hTPO assay is effective for identifying moderate to strong TPO inhibitors.
- It offers improved human relevance and reduced false positives compared to rat TPO assays.
- Further improvements may be needed to detect weak TPO inhibitors.
