Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
|
pubmed:dateCreated |
1992-4-28
|
pubmed:abstractText |
The effects of a number of phenobarbital-type inducers on selected drug-metabolizing enzymes in male F344/NCr rats were determined by measuring specific catalytic activities and/or by measuring the levels of RNA which hybridize with specific probes for the corresponding genes. The effects on hepatic CYP2B1 were assessed by measuring the levels of CYP2B1-specific RNA and benzyloxyresorufin O-dealkylase and testosterone 16 beta-hydroxylase activities. Levels of CYP3A were monitored by measuring the rate of hydroxylation of testosterone at the 6 beta-position. Microsomal epoxide hydrolase activity was determined by measurement of cellular RNA specific for this form and by assaying the hydrolysis of benzo[a]pyrene-4,5-oxide. UDP-glucuronyltransferase activity was assayed by measuring the glucuronidation of 3-hydroxybenz[a]anthracene. Levels of glutathione S-transferase Ya/Yc were measured by quantifying total cellular RNA coding for the proteins. When male F344/NCr rats were administered various doses of phenobarbital or dichlorodiphenyltrichloroethane (DDT), strong correlations between the induction of CYP2B1 and the induction of epoxide hydrolase or UDP-glucuronyltransferase activities were observed. Treatment of rats with barbiturates, hydantoins, halogenated pesticides such as DDT or alpha-hexachlorocyclohexane, 2,4,5,2',4',5'-hexachlorobiphenyl, CYP2B1 inhibitors such as clotrimazole or clonazepam, or such structurally-diverse compounds as 2-hexanone or diallyl sulfide resulted in induction of CYP2B1-mediated enzyme activity and induction of certain other forms of cytochrome P450, microsomal epoxide hydrolase, at least one form of UDP-glucuronyltransferase, and multiple forms of glutathione S-transferase. This suggests that, as a class, compounds which induce CYP2B1 also induce a coordinate hepatic pleiotropic response which includes induction of these other phase I and phase II drug-metabolizing enzymes.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Hydroxylases,
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/DDT,
http://linkedlifedata.com/resource/pubmed/chemical/Epoxide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Glucuronosyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotide Probes,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/Phenobarbital,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Steroid Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Xenobiotics,
http://linkedlifedata.com/resource/pubmed/chemical/testosterone 7-alpha-hydroxylase...
|
pubmed:status |
MEDLINE
|
pubmed:month |
Mar
|
pubmed:issn |
0006-2952
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
3
|
pubmed:volume |
43
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1067-78
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:1372805-Animals,
pubmed-meshheading:1372805-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:1372805-Base Sequence,
pubmed-meshheading:1372805-Cytochrome P-450 CYP1A1,
pubmed-meshheading:1372805-Cytochrome P-450 Enzyme System,
pubmed-meshheading:1372805-DDT,
pubmed-meshheading:1372805-Enzyme Induction,
pubmed-meshheading:1372805-Epoxide Hydrolases,
pubmed-meshheading:1372805-Glucuronosyltransferase,
pubmed-meshheading:1372805-Glutathione Transferase,
pubmed-meshheading:1372805-Liver,
pubmed-meshheading:1372805-Male,
pubmed-meshheading:1372805-Molecular Sequence Data,
pubmed-meshheading:1372805-Oligonucleotide Probes,
pubmed-meshheading:1372805-Oxidoreductases,
pubmed-meshheading:1372805-Phenobarbital,
pubmed-meshheading:1372805-RNA,
pubmed-meshheading:1372805-Rats,
pubmed-meshheading:1372805-Rats, Inbred F344,
pubmed-meshheading:1372805-Steroid Hydroxylases,
pubmed-meshheading:1372805-Xenobiotics
|
pubmed:year |
1992
|
pubmed:articleTitle |
A pleiotropic response to phenobarbital-type enzyme inducers in the F344/NCr rat. Effects of chemicals of varied structure.
|
pubmed:affiliation |
Laboratory of Comparative Carcinogenesis, NCI-Frederick Cancer Research and Development Center, MD 21702.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|