Journal article
Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: Structure-activity rules
Chemico-biological interactions, Vol.30(3), pp.271-285
1980
DOI: 10.1016/0009-2797(80)90050-2
PMID: 6769597
Abstract
A number of highly purified polychlorinated biphenyl (PCB) isomers and congeners were synthesized and administered to male Wistar rats at dosage levels of 30 and 150 μmol · kg
−1. The effects of this in vivo treatment on the drug-metabolizing enzymes were determined by measuring the microsomal benzo[
a]pyrene (B[
a]P) hydroxylase, dimethylaminoantipyrine (DMAP)
N-demethylase and NADPH-cytochrome
c reductase enzyme activities, the cytochrome
b
5 content and the relative peak intensities and spectral shifts of the reduced microsomal cytochrome
P-450: CO and ethylisocyanide (EIC) binding difference spectra. The results were compared to the effects of administering phenobarbitone (PB), 3-methylcholanthrene (MC) and PB plus MC (coadministered) to the test animals. The synthetic PCB congeners used in this study included 3,4,4′,5-tetrachlorobiphenyl (TCBP-1), 2,3′,4,4′-tetrachlorobiphenyl (TCBP-2), 2,3′,4,4′,5′-pentachlorobiphenyl (PCBP-1), 2,3,4,4′,5-pentachlorobiphenyl (PCBP-2), 2,3,3′,4,4′,5-hexachlorobiphenyl (HCBP-1), 2,3,3′,4′,5,6-hexachlorobiphenyl (HCBP-2), 2,3,3′,5,5′,6-hexachlorobiphenyl (HCBP-3), 2,2′,3,5,5′,6-hexachlorobiphenyl (HCBP-4) and 2,3,3′,4,5,5′-hexachlorobiphenyl (HCBP-5) and were used to reappraise the structure-activity rules for PCBs as hepatic microsomal enzyme inducers. The results suggested that (a) PCBs which induce MC or mixed-type activity must be substituted at both
para positions, at least two
meta positions but not necessarily on the same phenyl ring and can also contain one
ortho chloro substituent; (b) due to the considerable structural diversity of the PB-type inducers the rules for induction of this activity by PCB congeners are not readily defined.
Details
- Title: Subtitle
- Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: Structure-activity rules
- Creators
- A. Parkinson - University of Michigan–Ann ArborL. Robertson - University of GuelphLorna Safe - University of Michigan–Ann ArborS. Safe - University of Michigan–Ann Arbor
- Resource Type
- Journal article
- Publication Details
- Chemico-biological interactions, Vol.30(3), pp.271-285
- Publisher
- Elsevier Ireland Ltd
- DOI
- 10.1016/0009-2797(80)90050-2
- PMID
- 6769597
- ISSN
- 0009-2797
- eISSN
- 1872-7786
- Language
- English
- Date published
- 1980
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9984363665502771
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