April 18, 2023
Journal Article

Coupling environmental whole mixture toxicity screening with unbiased RNA-seq reveals site-specific biological responses in zebrafish

Abstract

Passive Sampling device (PSD) extracts paired with developmental toxicity assays in Danio Rerio (zebrafish) are excellent sensors for whole mixture toxicity associated with the bioavailable non-polar organics at environmental sites. We expand this concept by incorporating RNAseq in 48-hour post fertilization zebrafish statically exposed to PSD extracts from two Portland Harbor Superfund Site locations: river mile 6.5W (RM 6.5W) and river mile 7W (RM 7W). RM 6.5W contained higher concentrations of polycyclic aromatic hydrocarbons (PAHs), but diagnostic ratios of both extracts indicated similar PAH sourcing and composition. Developmental screens determined RM 6.5W to be more toxic with the most sensitive endpoint being a “wavy” notochord malformation. Differential gene expression from exposures to both extracts were largely parallel although more pronounced for RM 6.5W. When compared to the gene expression associated with individual chemical exposures, PSD extracts produced some gene signatures parallel to PAHs but were more closely matched by oxygenated-PAHs. Additionally, differential expression reminiscent of the wavy notochord phenotype was not accounted for by either class of chemical indicating the potential of other contaminants driving mixture toxicity. These techniques offer a compelling method for non-targeted hazard characterization of whole mixtures in an in-vivo vertebrate system without requiring complete chemical characterization.

Published: April 18, 2023

Citation

Rude C.I., L.G. Tidwell, S.C. Tilton, K.M. Waters, K.A. Anderson, and R.L. Tanguay. 2023. Coupling environmental whole mixture toxicity screening with unbiased RNA-seq reveals site-specific biological responses in zebrafish. Toxics 11, no. 3:Art. No. 201. PNNL-SA-181375. doi:10.3390/toxics11030201

Research topics