TY - JOUR
T1 - Potent induction of rat liver microsomal, drug-metabolizing enzymes by 2,3,3′,4,4′,5-hexabromobiphenyl, a component of fireMaster
AU - Robertson, L. W.
AU - Parkinson, A.
AU - Bandiera, S.
AU - Safe, S.
N1 - Funding Information:
The authors wish to express their appreciation to Mr. H.S. McKinnon for the MS, Dr. A. Woon-Fat for the PMR spectroscopy, L. Uhlig for the electrophoretic separations, K. Bonvie and C. Abrams for technical assistance during the syntheses, Dr. M. Mullin, Large Lakes Research Station, U.S.E.P.A. for the capillary GC quantitation of HBBp in fireMaster and Dr. A.B. Okey, Clinical Pharmacology Unit, Hospital for Sick Children, University of Toronto, for his advice and assistance with the receptor binding studies. The financial assistance of the Research Programs Directorate, Health and Welfare Canada (606-1444-X), the National Cancer Institute (5 R01-CA21814-02), the Natural Sciences and Engineering Research Council of Canada and the U.S. Environmental Protection Agency (CR 806928010) is gratefully acknowledged.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1981/4
Y1 - 1981/4
N2 - 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.
AB - 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.
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U2 - 10.1016/0009-2797(81)90060-0
DO - 10.1016/0009-2797(81)90060-0
M3 - Article
C2 - 6258818
AN - SCOPUS:0019515014
VL - 35
SP - 13
EP - 24
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
SN - 0009-2797
IS - 1
ER -