Sensitivity to Dioxin Decreases as Zebrafish Mature

Lanham, K.A., Peterson, R.E., and Heideman, W.
Toxicological sciences : an official journal of the Society of Toxicology   127(2): 360-370 (Journal)
Registered Authors
Heideman, Warren, Peterson, Richard E.
persistent organic chemicals agents, polycyclic aromatic hydrocarbons agents, aquatic toxicology environmental toxicology, transciption factors gene expression/regulation, aging reproductive & developmental toxicology, developmental toxicity, post-natal reproductive & developmental toxicology
MeSH Terms
  • Abnormalities, Drug-Induced*
  • Age Factors
  • Animals
  • Animals, Genetically Modified
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Embryo, Nonmammalian/pathology
  • Gene Expression Profiling/methods
  • Gene Expression Regulation, Developmental/drug effects
  • Green Fluorescent Proteins/biosynthesis
  • Green Fluorescent Proteins/genetics
  • Heart/drug effects*
  • Heart/embryology
  • Heart Defects, Congenital/chemically induced*
  • Heart Defects, Congenital/embryology
  • Heart Defects, Congenital/genetics
  • Heart Defects, Congenital/metabolism
  • Lethal Dose 50
  • Myosin Light Chains/genetics
  • Oligonucleotide Array Sequence Analysis
  • Reaction Time/drug effects
  • Receptors, Aryl Hydrocarbon/drug effects
  • Receptors, Aryl Hydrocarbon/genetics
  • Receptors, Aryl Hydrocarbon/metabolism
  • Transcription, Genetic/drug effects
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
22403156 Full text @ Toxicol. Sci.

The embryos of teleost fish are exquisitely sensitive to the toxic effects of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, several lines of evidence suggest that adults are less sensitive to TCDD. To better understand and characterize this difference between early life stage and adults, we exposed zebrafish (Danio rerio) to graded TCDD concentrations at different ages. The LD50 for embryos exposed at 1 day post fertilization (dpf) was more than an order of magnitude lower than it was for juveniles exposed at 30 dpf. The latency between exposure and response also increased with age. Embryo toxicity was characterized by marked cardiovascular collapse and heart malformation, while juveniles exposed at 30 dpf had no detectable cardiovascular toxicity. In juveniles the effects of TCDD exposure included stunted growth, altered pigmentation, and skeletal malformations. Furthermore, the transcriptional profile produced in hearts exposed to TCDD as embryos had very little overlap with the transcriptional changes induced by TCDD at 30 dpf. The early cardiotoxic response was associated with fish exposed prior to metamorphosis from the larval to the adult body plan at approximately 14 dpf. Our results show conclusively that the developmental stage at the time of exposure controls the toxic response to TCDD.

Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes