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Updated: Jun 8, 2026
09:01
A High-throughput Assay for the Prediction of Chemical Toxicity by Automated Phenotypic Profiling of Caenorhabditis elegans
Published on: March 14, 2019
In vitro screening for population variability in chemical toxicity
Shannon H O'Shea1, John Schwarz, Oksana Kosyk
1Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Summary
This study used human cell lines to test responses to environmental chemicals, finding significant variability in toxicity for some substances like PFOA. While heritability wasn't proven, the approach helps identify high-risk chemicals and genetic factors in toxicity.
Area of Science:
- Toxicology
- Genetics
- Environmental Health
Background:
- Immortalized human lymphoblastoid cell lines serve as in vitro models to identify genetic factors influencing xenobiotic responses.
- Investigative toxicology aims to assess interindividual and population-wide variability and heritability of chemical-induced toxicity phenotypes.
Purpose of the Study:
- To develop predictive, in vitro, genetics-anchored models for chemical-induced toxicity.
- To assess variability and heritability of toxicity responses using genetically diverse human cell lines.
Main Methods:
- Utilized Centre d'Etude du Polymorphisme Humain (CEPH) trio cell lines from the HapMap Consortium.
- Exposed cell lines to 14 environmental chemicals at three concentrations, assessing ATP production and caspase-3/7 activity.
- Employed replicate analyses to evaluate experimental variability and classify responses.
Main Results:
- Demonstrated interindividual variability in response to certain chemicals, notably perfluorooctanoic acid (PFOA) and phenobarbital.
- Did not find evidence for broad-sense heritability of toxicity response phenotypes with the tested chemicals.
- Identified substantial cell line variation and investigated candidate genetic factors for PFOA response variability using genome-wide association analysis.
Conclusions:
- Screening chemicals for toxicity in a genetically defined, diverse in vitro human cell system can identify high-risk chemicals.
- This approach helps determine within-species variability in chemical susceptibility.
- Potential genetic loci contributing to chemical susceptibility can be identified.
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