TY - JOUR
T1 - Induction of drug-metabolizing enzymes by fractionated commercial polybrominated biphenyls (PBBs)
AU - Robertson, L.
AU - Parkinson, A.
AU - Safe, S.
N1 - Funding Information:
The authors wish to thank Mr. H. S. McKinnon for his help in obtaining the GC-MS data, Dr. John Holt, Department of Mathematics and Statistics, University of Guelph, for his help in the statistical analyses of the data in Table 3, and the Research Programs Directorate, Health and Welfare Canada (606-1444-X), the National Cancer Institute (5 ROl-CA2181402), the Natural Sciences and Engineering Research Council of Canada, and the Environmental Protection Agency (CR 806928010) for financial assistance.
PY - 1981/2
Y1 - 1981/2
N2 - 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.
AB - 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.
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U2 - 10.1016/0041-008X(81)90287-8
DO - 10.1016/0041-008X(81)90287-8
M3 - Article
C2 - 6261418
AN - SCOPUS:0019427799
VL - 57
SP - 254
EP - 262
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 2
ER -