Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: Effects of di- ortho substitution

A Parkinson; L.W Robertson; Lorna Safe; S Safe

doi:10.1016/0009-2797(81)90059-4

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Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: Effects of di- ortho substitution

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Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: Effects of di- ortho substitution

A Parkinson, L.W Robertson, Lorna Safe and S Safe

Chemico-biological interactions, Vol.35(1), pp.1-12

1981

DOI: 10.1016/0009-2797(81)90059-4

PMID: 6781768

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Abstract

All of the 13 possible polychlorinated biphenyl (PCB) isomers and congeners substituted at both para positions, at least two meta positions (but not necessarily on the same ring) and at two ortho positions have been synthesized and tested as rat hepatic microsomal enzyme inducers. The effects of these compounds were evaluated by measuring microsomal benzo[ a]pyrene (B[ a]P) hydroxylase, 4-chlorobiphenyl (4-CBP) hydroxylase, 4-dimethylaminoantipyrine (DMAP) N-demethylase and NADPH-cytochrome c reductase activities, the cytochrome b 5 content and the relative peak intensities and spectral shifts of the carbon monoxide(CO)- and ethylisocyanide(EIC)-difference spectra of ferrocytochrome P-450. The results were compared to the effects of administering phenobarbitone (PB), 3-methylcholanthrene (MC) and PB plus MC (coadministered). At dose levels of 150 μmol · kg −1, all of the PCB congeners, except 2,3′,4,4′,5′,6-hexachlorobiphenyl, significantly enhanced hepatic microsomal cytochrome P-450 content, B[ a]P hydroxylase and/or DMAP N-demethylase activities compared to the control (corn oil-treated) animals. Only 5 of these compounds, namely 2,3,4,4′,5,6-hexa-, 2,2′,3,3′,4,4′-hexa-, 2,2′,3′,4,4′,5-hexa-, 2,3,3′,4,4′,6-hexa- and 2,2′,3,3′,4,4′,5-heptachlorobiphenyl, enhanced microsomal B[ a]P hydroxylase, 4-CBP hydroxylase, NADPH-cytochrome c reductase and DMAP N-demethylase activities in a manner consistent with a mixed pattern of induction. The results suggest that PCB isomers and congeners substituted at both para positions, at least two meta positions, at two ortho positions and containing a 2,3,4-trichloro substitution pattern on one ring are mixed-type inducers; in addition the effects of 2,3,4,4′,5,6-hexachlorobiphenyl were also consistent with a mixed pattern of induction.

PMR

TCDF

4-CBP

TLC

EIC

B[ a]P

GLC

Details

Title: Subtitle: Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: Effects of di- ortho substitution
Creators: A Parkinson - School of Public Health, The University of Michigan, Ann Arbor, MI 48109 U.S.A
L.W Robertson - The Guelph-Waterloo Centre for Graduate Work in Chemistry, Department of Chemistry, University of Guelph, Guelph, Ontario N1G 2W1 Canada
Lorna Safe - School of Public Health, The University of Michigan, Ann Arbor, MI 48109 U.S.A
S Safe - School of Public Health, The University of Michigan, Ann Arbor, MI 48109 U.S.A
Resource Type: Journal article
Publication Details: Chemico-biological interactions, Vol.35(1), pp.1-12
DOI: 10.1016/0009-2797(81)90059-4
PMID: 6781768
NLM abbreviation: Chem Biol Interact
ISSN: 0009-2797
eISSN: 1872-7786
Publisher: Elsevier Ireland Ltd
Language: English
Date published: 1981
Academic Unit: Occupational and Environmental Health
Record Identifier: 9984002367602771

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