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Transcriptome-Wide Prediction and Measurement of Combined Effects Induced by Chemical Mixture Exposure in Zebrafish
A Schüttler1,2, G Jakobs1, J M Fix1
1Department Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany.
Environmental Health Perspectives
|April 7, 2021
Summary
Predicting chemical mixture effects on gene expression is possible using concentration addition. This approach helps assess molecular impacts of environmental exposures and aids risk assessment.
Area of Science:
- Environmental toxicology
- Transcriptomics
- Computational biology
Background:
- Organisms face constant exposure to complex chemical mixtures.
- Understanding combined chemical effects is crucial for risk assessment.
- Omics technologies provide molecular insights into chemical exposures.
Purpose of the Study:
- To investigate the predictability of chemical mixture effects on the whole-transcriptome scale.
- To compare predicted and measured toxicogenomic responses in zebrafish embryos.
Main Methods:
- Used zebrafish embryos for toxicogenomic measurements.
- Applied the concentration addition concept to predict mixture effects.
- Predicted and measured whole-transcriptome responses to a mixture of diuron, diclofenac, and naproxen.
Main Results:
- Concentration addition provided reasonable estimates for mixture effects on the whole transcriptome.
- Observed multicomponent-driven effects for mixture components with similar and dissimilar modes of action.
- Nonadditive effects were occasionally observed.
Conclusions:
- Chemical mixture effects at the whole-transcriptome scale can be predicted using a concentration- and time-resolved approach.
- Improved molecular-level assessment of mixture exposures is achievable.
- Findings have relevance for risk assessment and pharmacological applications.
