PUBLICATION

Defects in cardiac function precede morphological abnormalities in fish embryos exposed to polycyclic aromatic hydrocarbons

Authors
Incardona, J.P., Collier, T.K., and Scholz, N.L.
ID
ZDB-PUB-040415-6
Date
2004
Source
Toxicology and applied pharmacology   196(2): 191-205 (Journal)
Registered Authors
Incardona, John P., Scholz, Nat
Keywords
Petroleum, Oil spill, Fish development, Heart morphogenesis, silent heart gene, CYP1A
MeSH Terms
  • Abnormalities, Drug-Induced/etiology*
  • Animals
  • Cardiovascular Abnormalities/chemically induced*
  • Embryonic and Fetal Development/drug effects*
  • Female
  • Fluorescent Antibody Technique
  • Heart/anatomy & histology
  • Heart/drug effects
  • Heart/embryology*
  • Heart Rate/drug effects
  • Heart Rate/physiology
  • Kidney/anatomy & histology
  • Kidney/embryology
  • Kidney/physiopathology
  • Male
  • Microscopy, Interference
  • Mutagens/toxicity
  • Petroleum/toxicity
  • Polycyclic Aromatic Hydrocarbons/toxicity*
  • Troponin T/genetics
  • Troponin T/metabolism
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish/anatomy & histology
  • Zebrafish/embryology*
  • Zebrafish/metabolism
PubMed
15081266 Full text @ Tox. App. Pharmacol.
CTD
15081266
Abstract
Fish embryos exposed to complex mixtures of polycyclic aromatic hydrocarbons (PAHs) from petrogenic sources show a characteristic suite of abnormalities, including cardiac dysfunction, edema, spinal curvature, and reduction in the size of the jaw and other craniofacial structures. To elucidate the toxic mechanisms underlying these different defects, we exposed zebrafish (Danio rerio) embryos to seven non-alkylated PAHs, including five two- to four-ring compounds that are abundant in crude oil and two compounds less abundant in oil but informative for structure-activity relationships. We also analyzed two PAH mixtures that approximate the composition of crude oil at different stages of weathering. Exposure to the three-ring PAHs dibenzothiophene and phenanthrene alone was sufficient to induce the characteristic suite of defects, as was genetic ablation of cardiac function using a cardiac troponin T antisense morpholino oligonucleotide. The primary etiology of defects induced by dibenzothiophene or phenanthrene appears to be direct effects on cardiac conduction, which have secondary consequences for late stages of cardiac morphogenesis, kidney development, neural tube structure, and formation of the craniofacial skeleton. The relative toxicity of the different mixtures was directly proportional to the amount of phenanthrene, or the dibenzothiophene-phenanthrene total in the mixture. Pyrene, a four-ring PAH, induced a different syndrome of anemia, peripheral vascular defects, and neuronal cell death, similar to the effects previously described for potent aryl hydrocarbon receptor ligands. Therefore, different PAH compounds have distinct and specific effects on fish at early life history stages.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping