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  • 1
    ISSN: 1432-0738
    Schlagwort(e): 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
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-0738
    Schlagwort(e): 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 ; Plasma tryptophan ; Ethoxyresorufin O-deethylase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Male Sprague-Dawley rats were treated with an LD20, an LD50, and an LD80 of 2,3,7,8-tetrachlorodibenzop-dioxin (tetra-CDD), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (penta-CDD), 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (hexa-CDD), 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (hepta-CDD), respectively, and a mixture of the four homologues where each CDD was represented at one-fourth its previously established LD20, LD50, and LD80, respectively. Plasma tryptophan levels, liver ethoxyresorufin O-deethylase (EROD) activities, and liver weights were determined at 2 and 8 days after treatment. Plasma tryptophan levels were dose-dependently elevated, particularly at 8 days after treatment, by as much as 75% over control levels. EROD activity in CDD-treated animals was induced 27- to 28-fold, as compared with vehicle-treated controls, but did not show any dose-response. Liver weights were also significantly increased by the CDD treatments, but the increase was not dose related. There was no correlation between plasma tryptophan levels, a biomarker of acute toxicity of CDDs, and EROD activity, a biomarker of arylhydrocarbon (Ah) receptor-mediated enzyme induction. It is concluded that the acute toxicity of CDDs, which correlates and shows perfect structure-activity relationship with reduced activities of key enzymes of intermediary metabolism, and the induction of enzymes by much lower doses of CDDs in the liver, have different mechanisms of action.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-1335
    Schlagwort(e): Carcinogen ; Benzo(a)pyrene ; DNA binding ; Enzyme induction ; Aryl hydrocarbon monooxygenase ; Epoxide hydrolase ; Glutathione S-transferase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Groups of four adult male rats [ZUR:SIV-Z] were pretreated with corn oil (control; 2ml/kg/day i.p. for 3 days), trans-stilbene-oxide (SO; 200 mg/kg/day i.p. for 2 days), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 10 μg/kg i.p. once, 4 days before killing), phenobarbital (PB; 1 g/liter in the drinking water for 8 days), and dieldrin (20 mg/kg/day i.p. for 3 or 9 days). They received an injection of [G-3H]benzo(a)pyrene (BaP, 31 μg/kg, 7.4·109 dpm/kg;i.v.) 16 h before killing. In the liver of each rat, five enzymatic activities and the covalent binding of BaP to DNA have been determined. The microsomal aryl hydrocarbon monooxygenase activity (AHM) ranged from 75% of control (SO) to 356% (TCDD), the nuclear AHM from 63% (SO) to 333% (TCDD). Microsomal epoxide hydrolase activity (EH) was induced up to 238% (PB), nuclear EH ranged from 86% (TCDD) to 218% (PB). A different extent of induction was observed in the two compartments. Highest induction of glutathione S-epoxide transferase activity (GST) was found with PB (202%). The DNA binding of BaP was modulated within 79% (dieldrin, 9 days) and 238% of control (TCDD). An enzyme digest of control DNA was analysed by Sephadex LH-20 chromatography. Multiple linear regression analysis with all data expressed as % of control yielded the following equation: DNA Binding= 1.49· Microsomal AHM-1.07 · Nuclear AHM+0.33 · Microsomal EH-0.52 · Nuclear EH+0.11 · Cytoplasmic GST+58.2. From this analysis it is concluded that (1) AHM located in the endoplasmic reticulum is most important in the formation of DNA-binding metabolites, (2) EH in the same compartment is not determinative in this respect nor has it a protective effect, (3) both membrane-bound enzyme activities located in the nucleus may inactivate potential ultimate carcinogens, and (4) cytoplasmic GST probably cannot reduce DNA binding due to its subcellular localization.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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