DIFFERENTIAL POTENCY OF ATROPISOMERS OF POLYCHLORINATED-BIPHENYLS ON CYTOCHROME-P450 INDUCTION AND UROPORPHYRIN ACCUMULATION IN THE CHICK-EMBRYO HEPATOCYTE CULTURE

RODMAN, LE and SHEDLOFSKY, SI and MANNSCHRECK, A and PUTTMANN, M and SWIM, AT and ROBERTSON, LW (1991) DIFFERENTIAL POTENCY OF ATROPISOMERS OF POLYCHLORINATED-BIPHENYLS ON CYTOCHROME-P450 INDUCTION AND UROPORPHYRIN ACCUMULATION IN THE CHICK-EMBRYO HEPATOCYTE CULTURE. BIOCHEMICAL PHARMACOLOGY, 41 (6-7). pp. 915-922. ISSN 0006-2952,

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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 N-demethylase (BPDM) activities were measured. The rank order of potency for total cytochrome P450 induction was HeCB > 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 > 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.

Item Type: Article
Uncontrolled Keywords: HEPATIC MICROSOMAL-ENZYMES; HALOGENATED BIPHENYLS; INDUCERS; CONGENERS; DECARBOXYLASE; INHIBITION; OXIDATION; ISOMERS; SYSTEM; PCBS;
Depositing User: Dr. Gernot Deinzer
Last Modified: 19 Oct 2022 08:46
URI: https://pred.uni-regensburg.de/id/eprint/55051

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