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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/0006-2952(91)90196-cDOI Listing

Publication Analysis

Top Keywords

erod activity
16
cytochrome p450
12
pecb ocb
12
p450 induction
8
chick embryo
8
embryo hepatocyte
8
hepatocyte culture
8
cytochromes p450
8
bpdm activities
8
hecb greater
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!