ISSN:
1432-0738
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
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01970672
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