The biologic and toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin in chickens

T. Sawyer, D. Jones, K. Rosanoff, G. Mason, J. Piskorska-Pliszczynska, S. Safe

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The administration of 2,3,7,8-TCDD to 2-week-old White Leghorn cockerels produced a dose-dependent induction of hepatic microsomal ethoxyresorufin O-deethylase (EROD) and benzo[α]pyrene (B[α]P) hydroxylase activities with induction EC50 values of 778 and 302 ng/kg, respectively. In addition, 2,3,7,8-TCDD also induced 4-dimethylaminoantipyrine (DMAP) N-demethylase (EC50 = 561 ng/kg), this result contrasting with studies reported for other animal species in which 2,3,7,8-TCDD either does not induce or inhibits this cytochrome P-450 dependent monooxygenase enzyme activity. However, the reduced cytochrome P-450 : CO binding difference spectral absorption maxima for the 2,3,7,8-TCDD induced microsomes was observed at 448 nm which was similar to that reported for most animals which have been investigated. Electrophoresis of control and 2,3,7,8-TCDD induced microsomal proteins using SDS polyacrylamide slab gels showed intensification of 3 protein staining bands at Mr 53 000, 56 000 and 58 000. Incubation of the 2,3,7,8-TCDD-induced microsomes with SKF-525A and α-naphthoflavone showed that both compounds inhibited DMAP N-demethylase, EROD and AHH and that α-naphthoflavone was the more potent inhibitor of all 3 microsomal monooxygenases. 2,3,7,8-TCDD treatment caused significant involution of the Bursa of Fabricius when administered at a dose level of 10 μg/kg for 3 days and this result confirmed the extreme sensitivity of the immature White Leghorn cockerel to the biologic and toxic effects elicited by 2,3,7,8-TCDD. However, in contrast to other sensitive species, no high affinity cytosolic receptor protein for [3H]2,3,7,8-TCDD could be detected in the liver of chick embryos or 2-week-old birds.

Original languageEnglish (US)
Pages (from-to)197-206
Number of pages10
JournalToxicology
Volume39
Issue number2
DOIs
StatePublished - May 1986

Keywords

  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin
  • Chicken
  • Cytosol receptor binding
  • Enzyme induction
  • Toxicity

ASJC Scopus subject areas

  • Toxicology

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