PuSH - Publication Server of Helmholtz Zentrum München: Comparative Toxicity of Four Chlorinated Dibenzo-p-dioxins (CDDs) and their Mixture. Part II: Structure-activity Relationships with Inhibition of Hepatic Phosphoenolpyruvate Carbocykinase, Pyruvate Carbocylase, and gamma-glutamyl Transpeptidase Activities.

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Weber, L.W.D. ; Lebofsky, M. ; Stahl, B.U. ; Kettrup, A. ; Rozman, K.K.

Comparative Toxicity of Four Chlorinated Dibenzo-p-dioxins (CDDs) and their Mixture. Part II: Structure-activity Relationships with Inhibition of Hepatic Phosphoenolpyruvate Carbocykinase, Pyruvate Carbocylase, and gamma-glutamyl Transpeptidase Activities.

Arch. Toxicol. 66, 478-483 (1992)

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Open Access Green as soon as Postprint is submitted to ZB.

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Male Sprague-Dawley rats were treated with an LD₂₀, LD₅₀ and LD₈₀ respectively, of tetra-, penta-, hexa-,hepta-CDD and a mixture of the four CDDs, all carrying chlorine substituents in the biologically crucial 2, 3, 7, and 8 positions. Specific activities of two key enzymes of gluconeogenesis, viz, phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC), as well as the activity of the preneoplastic marker enzyme γ-glutamyl transpeptidase (γ-GT), were determined in livers of CDD-treated and ad libitum-fed control animals. PEPCK activity showed evidence for dose-related inhibition on the second day after dosing; PC activity was slightly reduced, whereas γ-GT activity was dose-dependently inhibited. By 8 days after dosing PEPCK activities were dose-dependently decreased after administration of all four CDDs and their mixture. PC activities were significantly reduced, but no dose-response was evident. The activity of γ-GT was dosedependently inhibited, but only to a value of 25% below control activities. It is concluded that CDDs share a common mechanism of acute toxicity, viz, inhibition of glucocorticoid-dependent enzymes which results in a derailment of intermediary metabolism not compatible with survival of the animals.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords 2,3,7,8-Tetrachlorodibenzo-p-dioxin 1,2,3,7,8-Pentachlorodibenzo-p-dioxin 1,2,3,4,7,8-Hexachlorodibenzo-p-dioxin 1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin Mixture Structure-activity relationship Acute toxicity Phosphoenolpyruvate carboxykinase Pyruvate carboxylase γ-Glutamyl transpeptidase

ISSN (print) / ISBN 0340-5761

e-ISSN 1432-0738

Journal Archives of Toxicology

Quellenangaben Volume: 66, Issue: 7, Pages: 478-483

Publisher Springer

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Molecular Toxicology and Pharmacology (TOX)