Statements in which the resource exists as a subject.
PredicateObject
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.