TitleCoupling Environmental Whole Mixture Toxicity Screening with Unbiased RNA-Seq Reveals Site-Specific Biological Responses in Zebrafish.
Publication TypeJournal Article
Year of Publication2023
AuthorsRude, CI, Tidwell, LG, Tilton, SC, Waters, KM, Anderson, KA, Tanguay, RL
Date Published2023 Feb 21

Passive sampling device (PSD) extracts paired with developmental toxicity assays in (zebrafish) are excellent sensors for whole mixture toxicity associated with the bioavailable non-polar organics at environmental sites. We expand this concept by incorporating RNA-Seq in 48-h 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 the 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 exposure to both extracts was 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.

Alternate JournalToxics
PubMed ID36976966
PubMed Central IDPMC10053777
Grant ListP30 ES030287 / NH / NIH HHS / United States
P42 ES016465 / NH / NIH HHS / United States
T32 ES007060 / NH / NIH HHS / United States