PUBLICATION

Transcriptional impact of organophosphate and metal mixtures on olfaction: Copper dominates the chlorpyrifos-induced response in adult zebrafish

Authors
Tilton, F.A., Tilton, S.C., Bammler, T.K., Beyer, R.P., Stapleton, P.L., Scholz, N.L., and Gallagher, E.P.
ID
ZDB-PUB-110317-4
Date
2011
Source
Aquatic toxicology (Amsterdam, Netherlands)   102(3-4): 205-215 (Journal)
Registered Authors
Gallagher, Evan P., Scholz, Nat, Tilton, Fred, Tilton, Susan C.
Keywords
Copper, Chlorpyrifos, Organophosphate pesticide, Zebrafish, Olfaction, Toxicity, Mixtures
Datasets
GEO:GSE47039
MeSH Terms
  • Animals
  • Biomarkers/metabolism
  • Chlorpyrifos/toxicity*
  • Copper/toxicity*
  • Female
  • Gene Expression/drug effects
  • Insecticides/toxicity*
  • Male
  • Nervous System/drug effects
  • Olfactory Pathways/drug effects
  • Olfactory Pathways/metabolism
  • Smell/drug effects*
  • Smell/genetics
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
21356183 Full text @ Aquat. Toxicol.
CTD
21356183
Abstract
Chemical exposures in fish have been linked to loss of olfaction leading to an inability to detect predators and prey and decreased survival. However, the mechanisms underlying olfactory neurotoxicity are not well characterized, especially in environmental exposures which involve chemical mixtures. We used zebrafish to characterize olfactory transcriptional responses by two model olfactory inhibitors, the pesticide chlorpyrifos (CPF) and mixtures of CPF with the neurotoxic metal copper (Cu). Microarray analysis was performed on RNA from olfactory tissues of zebrafish exposed to CPF alone or to a mixture of CPF and Cu. Gene expression profiles were analyzed using principal component analysis and hierarchical clustering, whereas gene set analysis was used to identify biological themes in the microarray data. Microarray results were confirmed by real-time PCR on genes serving as potential biomarkers of olfactory injury. In addition, we mined our previously published Cu-induced zebrafish olfactory transcriptional response database (Tilton et al., 2008) for the purposes of discriminating pathways of olfaction impacted by either the individual agents or the CPF-Cu mixture transcriptional signatures. CPF exposure altered the expression of gene pathways associated with cellular morphogenesis and odorant binding, but not olfactory signal transduction, a known olfactory pathway for Cu. The mixture profiles shared genes from the Cu and CPF datasets, whereas some genes were altered only by the mixtures. The transcriptional signature of the mixtures was more similar to that in zebrafish exposed to Cu alone than for CPF. In conclusion, exposure to a mixture containing a common environmental metal and pesticide causes a unique transcriptional signature that is heavily influenced by the metal, even when organophosphate predominates.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping