Potent induction of rat liver microsomal, drug-metabolizing enzymes by 2,3,3′,4,4′,5-hexabromobiphenyl, a component of fireMaster

L. W. Robertson, A. Parkinson, S. Bandiera, S. Safe

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)13-24
Number of pages12
JournalChemico-Biological Interactions
Volume35
Issue number1
DOIs
StatePublished - Apr 1981
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology

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