Document Detail


Potent induction of rat liver microsomal, drug-metabolizing enzymes by 2,3,3',4,4',5-hexabromobiphenyl, a component of fireMaster.
MedLine Citation:
PMID:  6258818     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The multistep synthesis and purification of 2,3,3',4,4',5-hexabromobiphenyl (HBBp) is described. Capillary gas chromatography revealed that HBBp comprises 0.05% of the industrial polybrominated biphenyl (PBB) mixture, fireMaster BP-6 (lot 7062). When administered to immature male Wistar rats, HBBp caused a dose-dependent increase in (a) the activity of benzo[a]pyrene (B[a]P) hydroxylase (AHH) and 4-chlorobiphenyl (4-CBP) hydroxylase and (b) the concentration of cytochrome P-450. Sodium dodecyl sulfate (SDS)-gel electrophoresis indicated that these increases in cytochrome P-450 and cytochrome P-450-dependent monooxygenase activities were accompanied by a dose-dependent intensification of a protein of relative molecular weight (Mr) 55 000 which comigrated with the major 3-methylcholanthrene(MC)-inducible form of cytochrome P-450 (i.e., cytochrome P-448). Like MC, but in contrast to phenobarbitone (PB), HBBp competitively displaced 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin ([3H]-TCDD) from the cytosolic protein thought to be the receptor for cytochrome P-448 induction. The results indicate that HBBp is a potent inducer of cytochrome P-448 and as such is the third MC-type inducer identified in fireMaster BP-6.
Authors:
L W Robertson; A Parkinson; S Bandiera; S Safe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Chemico-biological interactions     Volume:  35     ISSN:  0009-2797     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  1981 Apr 
Date Detail:
Created Date:  1981-05-26     Completed Date:  1981-05-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  13-24     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Aryl Hydrocarbon Hydroxylases / biosynthesis
Biphenyl Compounds / pharmacology*
Cytochrome P-450 Enzyme System / metabolism
Cytochromes / metabolism
Enzyme Induction / drug effects*
Flame Retardants / chemical synthesis,  pharmacology*
Male
Methylcholanthrene / pharmacology
Microsomes, Liver / enzymology*
Phenobarbital / pharmacology
Polybrominated Biphenyls / chemical synthesis,  pharmacology*
Rats
Receptors, Aryl Hydrocarbon
Receptors, Drug / metabolism
Grant Support
ID/Acronym/Agency:
5 R01-CA21814-02)/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Biphenyl Compounds; 0/Cytochromes; 0/Flame Retardants; 0/Polybrominated Biphenyls; 0/Receptors, Aryl Hydrocarbon; 0/Receptors, Drug; 50-06-6/Phenobarbital; 56-49-5/Methylcholanthrene; 59536-65-1/Firemaster BP-6; 77607-09-1/2,3,3',4,4',5-hexabromobiphenyl; 79682-25-0/2,3,3',4,4'5,6-heptabromobiphenyl; 9035-50-1/cytochrome P-448; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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