Differential potency of atropisomers of polychlorinated biphenyls on cytochrome P450 induction and uroporphyrin accumulation in the chick embryo hepatocyte culture
| Autor: | Albrecht Mannschreck, Michael Püttmann, Larry E. Rodman, Alice T. Swim, Steven I. Shedlofsky, Larry W. Robertson |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Protoporphyrins
Stereoisomerism Chick Embryo Biochemistry Cytochrome P-450 Enzyme System Cytochrome P-450 CYP1A1 medicine Animals Potency Inducer Uroporphyrins Enzyme inducer Cells Cultured Pharmacology chemistry.chemical_classification Dose-Response Relationship Drug biology Cytochrome P450 Polychlorinated Biphenyls Molecular biology Enzyme medicine.anatomical_structure Liver chemistry Enzyme Induction Hepatocyte biology.protein Oxidoreductases Benzphetamine medicine.drug |
| Zdroj: | Biochemical Pharmacology. 41:915-922 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/0006-2952(91)90196-c |
| Popis: | The atropisomers of 2,2',3,4,6-pentachlorobiphenyl (PeCB), 2,2',3,4,4',6-hexachlorobiphenyl (HeCB), and 2,2',3,3',4,4',6,6'-octachlorobiphenyl (OCB) were studied in the chick embryo hepatocyte culture to determine if chirality plays a role in the recognition events associated with the induction of cytochromes P450 and the accumulation of uroporphyrin (URO). Concentration-related induction of cytochrome P450 content, ethoxyresorufin-O-deethylase (EROD) and benzphetamine N-demethylase (BPDM) activities were measured. The rank order of potency for total cytochrome P450 induction was HeCB greater than OCB greater than or equal to PeCB. The (+)- and (-)-enantiomers of PeCB and OCB were of equal potencies as inducers of cytochromes P450, whereas the (+)-HeCB was greater than the (-)-HeCB. HeCB was a much more potent inducer of EROD activity than was either PeCB or OCB. EROD activity was induced to a much greater extent by the (+)-enantiomers of all compounds, with the (-)-enantiomers of PeCB and OCB being inactive. BPDM activity was induced by all three compounds in the order of OCB greater than or equal to HeCB greater than PeCB. The (-)-enantiomers were more potent inducers of BPDM activities than were the (+)-enantiomers, except for HeCB, in which the (+)- was more potent than the (-)-enantiomer. Analysis of porphyrin accumulation in cultures treated with delta-aminolevulinic acid revealed that (+)-HeCB caused the greatest percent URO accumulation, which also correlated with the greatest increase in EROD activity. All other enantiomers caused up to 47% URO accumulation, which did not correlate with an increase in EROD activity. |
| Databáze: | OpenAIRE |
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