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Temporal induction of cytochrome p450 1a in the mirror carp (<i>Cyprinus carpio</i>) after administration of several polycyclic aromatic hydrocarbons
62
Citations
29
References
1994
Year
PharmacotherapyPhysiologically-based Pharmacokinetic ModelingToxicological MechanismMolecular PharmacologyToxicologyP450 1APolycyclic Aromatic HydrocarbonBiochemistryErod ActivitiesCytochrome P450 1AMirror CarpExperimental ToxicologyPharmacologyTemporal InductionBiologyNatural SciencesClinical Pharmacology7-Ethoxyresorufin O-deethylationMedicinePharmacokineticsDrug DiscoveryDrug Analysis
Abstract High inductions of 7-ethoxyresorufin O-deethylation (EROD) activities, cytochrome P450 1A protein levels (P4501 A), and total cytochrome P450 content (P450) were observed 1,2,5, and 14 d after a single i.p. injection of 99.5 μmol/kg benzo[a]py-rene (BaP) and chrysene (Chrys). The highest inductions in EROD activities and P450 1A protein levels were seen 2 d after treatment, approximately 35- and 11-fold relative to the controls. Less pronounced increases of EROD activities and P450 1A protein levels, approximately 3- to 10-fold and 6-fold, respectively, were observed after treatment with equimolar concentrations of flu-oranthene (Fluor) and pyrene (Pyr). Benzo[ghi]perylene (BghiP) and the carrier dimethyl sulfoxide (DMSO) did not affect these parameters. The highest concentrations of PAHs in the liver, equivalent to 2 to 25% of the dose, were found 1 or 2 d after treatment. The highest percentage of the dose in the liver was observed for Chrys, followed by BghiP, BaP, Fluor, and Pyr. Poor correlations were found between hepatic concentrations of PAHs and P450 1A increases, which might be attributed to the rapid metabolism of these compounds.
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