Induction of drug-metabolizing enzymes by fractionated commercial polybrominated biphenyls (PBBs)

L. Robertson, A. Parkinson, S. Safe

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

A commercial polybrominated biphenyl mixture was separated chromatographically into two fractions on neutral alumina (AA and AB) and into three fractions on Florisil (FA, FB, and FC) by sequential elution with solvents of increasing polarity. Using established methods, the activity of each fraction as hepatic microsomal cytochrome P-450- and/or cytochrome P-448-dependent monooxygenase enzyme inducers was examined in the male Wister rat. Like the coadministration of phenobarbitone and 3-methylcholanthrene, commercial PBBs, either unfractionated or reconstituted from its various fractions, induced both cytochromes P-450 and P-448. Both cytochromes were also induced by the less-polar fractions AA and FA. In contrast, little or no inductive effects were exhibited by the more polar Florisil fractions, FB and FC, indicating that the ability of commercial PBBs to induce cytochrome P-448 is not due to contaminating brominated dibenzofurans or dibenzodioxins. Unlike the polar Florisil fraction, the more polar alumina fraction, AB, was a potent microsomal enzyme inducer. This fraction was enriched in 2,3,3′,4,4′,5-hexa- and 2,2′,3,3′,4,4′,5-heptabromobiphenyl and also contained unassigned monochloro derivatives of a penta- and hexabromobiphenyl, namely C12H4Br5Cl and C12 H3Br6Cl, respectively. The data strongly suggest that the biologic effects of the commercial polybrominated biphenyl mixture are due to the various halogenated biphenyls present. These results are discussed in terms of the reported toxic potency of each PBB fraction and with reference to the known biologic activity of individual polybrominated biphenyl congeners or their chloro analogs.

Original languageEnglish (US)
Pages (from-to)254-262
Number of pages9
JournalToxicology and Applied Pharmacology
Volume57
Issue number2
DOIs
StatePublished - Feb 1981

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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