2,3,7,8-Tetrachlorodibenzo-p-dioxin elicits aryl hydrocarbon receptor-mediated apoptosis in the avian DT40 pre-B-cell line through activation of caspases 9 and 3

N. Puebla-Osorio, Kenneth Ramos, M. H. Falahatpisheh, R. Smith, L. R. Berghman

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The halogenated aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to induce immunotoxicity, but relatively little is known regarding its effects on B-lymphocytes, and on avian B-cells in particular. In this study, the avian bursal pre-B-cell line DT40 was exposed to TCDD ranging from 1 to 500 nM for 1 and 6 h. At 100 nM, TCDD caused a significant increase in the number of apoptotic cells, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assay, and induced the expression of the chicken cytochrome P450 1A4 (CYP1A4) mRNA, a hallmark of TCDD exposure. TCDD induced transient upregulation of aryl hydrocarbon receptor (AhR) mRNA. At 100 nM, both caspase 3 and caspase 9 were transiently upregulated after 1 h, but returned to normal levels after 6 h of exposure. Challenge with TCDD after AhR blockade with resveratrol, a competitive AhR antagonist, prevented changes in caspases 3 and 9 and in the AhR message itself, suggesting that the effects of TCDD were mediated via the AhR. TCDD did not cause significant changes in the relative gene expression of caspase 8, Bcl-2 and Bcl-xL. We conclude that avian DT40 pre-B-cells exposed to TCDD are susceptible to apoptosis, likely through activation of executioner caspase 3.

Original languageEnglish (US)
Pages (from-to)461-468
Number of pages8
JournalComparative Biochemistry and Physiology - C Toxicology and Pharmacology
Volume138
Issue number4
DOIs
Publication statusPublished - Aug 2004
Externally publishedYes

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Keywords

  • Apoptosis
  • Aryl hydrocarbon receptor
  • B-cell
  • Caspases
  • Chicken
  • DT40
  • Resveratrol
  • TCDD

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Health, Toxicology and Mutagenesis
  • Pharmacology

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