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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
19
|
| pubmed:dateCreated |
1983-11-23
|
| pubmed:abstractText |
Several polychlorinated biphenyl (PCB) isomers and congeners resemble phenobarbitone (PB) in their mode of induction of the hepatic drug-metabolizing enzymes; however, unlike PCBs which induce aryl hydrocarbon hydroxylase, no apparent structure-activity correlations have been reported. This study examines the effects of structure on the activity of a series of 2,4-dichloro-substituted biphenyls as inducers of several microsomal enzyme activities including dimethylaminoantipyrine N-demethylase, benzo[a]pyrene hydroxylase, aldrin epoxidase, and ethoxyresorufin O-deethylase. The results clearly illustrate a marked effect of structure on activity: all of the 2,4-dichloro-substituted PCBs resembled PB in their mode of induction. However, the potency of the induction response was dependent on the substitution pattern of the second phenyl ring (i.e. 2,3,4,5-tetrachloro greater than or equal to 2,3,4,5,6-pentachloro greater than 2,3,4,6-tetrachloro greater than 2,3,5,6-tetrachloro greater than 2,4,6-trichloro); the structure of the lower chlorinated ring also determined induction potency since the 2,4-dichloro-substituted PCBs were generally more active than their 4-chloro-substituted analogs, whereas the 2-substituted PCB homologs were inactive. The structural factors which typify the most active PB-type inducer, 2,2',3,4,4',5-hexachlorobiphenyl, include the presence of two para-, at least two meta- and two ortho-chloro substituents. In addition to the structure-activity correlations noted for PCBs, the 2,2',3,4,4',5-hexachlorobiphenyl congener also elicited a dose-response induction of two PB-inducible enzymes, aldrin epoxidase and dimethylaminoantipyrine N-demethylase.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzopyrene Hydroxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP1A1,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome b Group,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes b5,
http://linkedlifedata.com/resource/pubmed/chemical/Methylcholanthrene,
http://linkedlifedata.com/resource/pubmed/chemical/Mixed Function Oxygenases,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases, N-Demethylating,
http://linkedlifedata.com/resource/pubmed/chemical/Phenobarbital,
http://linkedlifedata.com/resource/pubmed/chemical/Polychlorinated Biphenyls,
http://linkedlifedata.com/resource/pubmed/chemical/aldrin epoxidase,
http://linkedlifedata.com/resource/pubmed/chemical/dimethylaminoantipyrine...
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0006-2952
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
32
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2955-63
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:6414484-Animals,
pubmed-meshheading:6414484-Benzopyrene Hydroxylase,
pubmed-meshheading:6414484-Cytochrome P-450 CYP1A1,
pubmed-meshheading:6414484-Cytochrome P-450 Enzyme System,
pubmed-meshheading:6414484-Cytochrome b Group,
pubmed-meshheading:6414484-Cytochromes b5,
pubmed-meshheading:6414484-Drug Interactions,
pubmed-meshheading:6414484-Enzyme Induction,
pubmed-meshheading:6414484-Male,
pubmed-meshheading:6414484-Methylcholanthrene,
pubmed-meshheading:6414484-Microsomes, Liver,
pubmed-meshheading:6414484-Mixed Function Oxygenases,
pubmed-meshheading:6414484-Oxidoreductases,
pubmed-meshheading:6414484-Oxidoreductases, N-Demethylating,
pubmed-meshheading:6414484-Phenobarbital,
pubmed-meshheading:6414484-Polychlorinated Biphenyls,
pubmed-meshheading:6414484-Rats,
pubmed-meshheading:6414484-Rats, Inbred Strains,
pubmed-meshheading:6414484-Structure-Activity Relationship
|
| pubmed:year |
1983
|
| pubmed:articleTitle |
Polychlorinated biphenyls as phenobarbitone-type inducers of microsomal enzymes. Structure-activity relationships for a series of 2,4-dichloro-substituted congeners.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|