Journal article
Differential potency of atropisomers of polychlorinated biphenyls on cytochrome P450 induction and uroporphyrin accumulation in the chick embryo hepatocyte culture
Biochemical pharmacology, Vol.41(6), pp.915-922
1991
DOI: 10.1016/0006-2952(91)90196-C
PMID: 1901208
Abstract
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
Ndemethylase (BPDM) activities were measured. The rank order of potency for total cytochrome P450 induction was HeCB > OCB ⩾ 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 ⩾ HeCB > 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 δ-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.
Details
- Title: Subtitle
- Differential potency of atropisomers of polychlorinated biphenyls on cytochrome P450 induction and uroporphyrin accumulation in the chick embryo hepatocyte culture
- Creators
- Larry E Rodman - Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506-0054, USASteven I Shedlofsky - Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506-0054, USAAlbrecht Mannschreck - Department of Organic Chemistry, University of Regensburg, D-8400 Regensburg, F.R.GMichael Püttmann - Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506-0054, USAAlice T Swim - Department of Veterans Affairs Medical Center, Division of Gastroenterology, Lexington, KY 40511, U.S.ALarry W Robertson - Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506-0054, USA
- Resource Type
- Journal article
- Publication Details
- Biochemical pharmacology, Vol.41(6), pp.915-922
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0006-2952(91)90196-C
- PMID
- 1901208
- ISSN
- 0006-2952
- eISSN
- 1873-2968
- Language
- English
- Date published
- 1991
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9984002462202771
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