Journal article
Polybrominated biphenyls as aryl hydrocarbon hydroxylase inducers: structure-activity correlations
Chemico-biological interactions, Vol.42(1), pp.53-66
1982
DOI: 10.1016/0009-2797(82)90141-7
PMID: 6295646
Abstract
The synthesis of all possible laterally-substituted polybrominated biphenyl (PBB) congeners containing two
para bromines is described. Using enzymic, electrophoretic and ligand-binding assays that distinguish between phenobarbitone(PB)- and 3-methylcholanthrene(MC)-type inducers, the synthetic PBBs were evaluated as inducers of liver microsomal drug-metabolizing enzymes in the immature male Wistar rat. 4,4′-Dibromobiphenyl resembled PB in its mode of induction whereas all the
meta-brominated derivatives of 4,4′-dibromobiphenyl, namely 3,4,4′-tri-, 3,4,4′,5-tetra-, 3,3′, 4,4′-tetra-, 3,3′,4,4′,5-penta- and 3,3′,4,4′,5,5′-hexabromobiphenyl, resembled MC in their mode of induction. The results obtained with 3,4,4′-tribromobiphenyl demonstrate that, in contrast to the polychlorinated biphenyls (PCBs), a single
meta halogen substituent is sufficient to abolish the PB-type characteristics of 4,4′-dibromobiphenyl and convert it to a strictly MC-type inducer. PBBs which induce AHH activity must be substituted at both
para positions and at one, two, three or four
meta positions.
Ortho-substitution of PBBs which contain only lateral bromine groups may also give compounds which are aryl hydrocarbon hydroxylase (AHH) inducers. One of the MC-type PBBs, namely 3,3′,4,4′-tetrabromobiphenyl, which has been tentatively identified in the commercial PBB mixture, fireMaster BP-6, was at least 50 times more potentias an inducer of AHH activity than the commercial PBB mixture. The induction of AHH by 3,3′,4,4′-tetrabromobiphenyl was accompanied by a dose-dependent decrease in both thymus and spleen weights. The thymus and/or spleen weights were decreased in rats treated with the other MC-type PBBs which further supports the correlation between the toxicity of the PBBs and their ability to induce AHH.
Details
- Title: Subtitle
- Polybrominated biphenyls as aryl hydrocarbon hydroxylase inducers: structure-activity correlations
- Creators
- L.W Robertson - Department of Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USAA Parkinson - Department of Biochemistry and Drug Metabolism, Hoffmann-La Roche, Inc., Nutley, NJ 07110 U.S.AM.A Campbell - The Guelph-Waterloo Centre for Graduate Work in Chemistry, Guelph Campus, Department of Chemistry, University of Guelph, Guelph, Ontario N1G 2W1 CanadaS Safe - Department of Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA
- Resource Type
- Journal article
- Publication Details
- Chemico-biological interactions, Vol.42(1), pp.53-66
- Publisher
- Elsevier Ireland Ltd
- DOI
- 10.1016/0009-2797(82)90141-7
- PMID
- 6295646
- ISSN
- 0009-2797
- eISSN
- 1872-7786
- Language
- English
- Date published
- 1982
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9984002438302771
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