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Dynamic gene expression changes precede dioxin-induced liver pathogenesis in medaka fish.

Publication ,  Journal Article
Volz, DC; Hinton, DE; Law, JM; Kullman, SW
Published in: Toxicological sciences : an official journal of the Society of Toxicology
February 2006

A major challenge for environmental genomics is linking gene expression to cellular toxicity and morphological alteration. Herein, we address complexities related to hepatic gene expression responses after a single injection of the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) and illustrate an initial stress response followed by cytologic and adaptive changes in the teleost fish medaka. Using a custom 175-gene array, we find that overall hepatic gene expression and histological changes are strongly dependent on dose and time. The most pronounced dioxin-induced gene expression changes occurred early and preceded morphologic alteration in the liver. Following a systematic search for putative Ah response elements (AHREs) (5'-CACGCA-3') within 2000 bp upstream of the predicted transcriptional start site, the majority (87%) of genes screened in this study did not contain an AHRE, suggesting that gene expression was not solely dependent on AHRE-mediated transcription. Moreover, in the highest dosage, we observed gene expression changes associated with adaptation that persisted for almost two weeks, including induction of a gene putatively identified as ependymin that may function in hepatic injury repair. These data suggest that the cellular response to dioxin involves both AHRE- and non-AHRE-mediated transcription, and that coupling gene expression profiling with analysis of morphologic pathogenesis is essential for establishing temporal relationships between transcriptional changes, toxicity, and adaptation to hepatic injury.

Duke Scholars

Published In

Toxicological sciences : an official journal of the Society of Toxicology

DOI

EISSN

1096-0929

ISSN

1096-6080

Publication Date

February 2006

Volume

89

Issue

2

Start / End Page

524 / 534

Related Subject Headings

  • Toxicology
  • Time Factors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Aryl Hydrocarbon
  • Polychlorinated Dibenzodioxins
  • Oryzias
  • Oligonucleotide Array Sequence Analysis
  • Male
  • Liver
  • Injections, Intraperitoneal
 

Citation

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Chicago
ICMJE
MLA
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Volz, D. C., Hinton, D. E., Law, J. M., & Kullman, S. W. (2006). Dynamic gene expression changes precede dioxin-induced liver pathogenesis in medaka fish. Toxicological Sciences : An Official Journal of the Society of Toxicology, 89(2), 524–534. https://doi.org/10.1093/toxsci/kfj033
Volz, David C., David E. Hinton, J McHugh Law, and Seth W. Kullman. “Dynamic gene expression changes precede dioxin-induced liver pathogenesis in medaka fish.Toxicological Sciences : An Official Journal of the Society of Toxicology 89, no. 2 (February 2006): 524–34. https://doi.org/10.1093/toxsci/kfj033.
Volz DC, Hinton DE, Law JM, Kullman SW. Dynamic gene expression changes precede dioxin-induced liver pathogenesis in medaka fish. Toxicological sciences : an official journal of the Society of Toxicology. 2006 Feb;89(2):524–34.
Volz, David C., et al. “Dynamic gene expression changes precede dioxin-induced liver pathogenesis in medaka fish.Toxicological Sciences : An Official Journal of the Society of Toxicology, vol. 89, no. 2, Feb. 2006, pp. 524–34. Epmc, doi:10.1093/toxsci/kfj033.
Volz DC, Hinton DE, Law JM, Kullman SW. Dynamic gene expression changes precede dioxin-induced liver pathogenesis in medaka fish. Toxicological sciences : an official journal of the Society of Toxicology. 2006 Feb;89(2):524–534.
Journal cover image

Published In

Toxicological sciences : an official journal of the Society of Toxicology

DOI

EISSN

1096-0929

ISSN

1096-6080

Publication Date

February 2006

Volume

89

Issue

2

Start / End Page

524 / 534

Related Subject Headings

  • Toxicology
  • Time Factors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Aryl Hydrocarbon
  • Polychlorinated Dibenzodioxins
  • Oryzias
  • Oligonucleotide Array Sequence Analysis
  • Male
  • Liver
  • Injections, Intraperitoneal