Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
1993-4-23
|
| pubmed:abstractText |
The effect of route of administration on the ability of indole-3-carbinol (13C), an anticarcinogen present in cruciferous vegetables, to induce estradiol 2-hydroxylase (EH) in female rat liver microsomes was investigated and compared to that of its main gastric conversion product, 3,3'-diindolylmethane (DIM). This dimer was more potent than 13C after either oral or intraperitoneal administration and was also a better in vitro inhibitor of EH in control and 13C-induced hepatic microsomes. The induction of both CYP1A1 and 1A2 in about equal amounts by 13C and DIM as well as of CYP2B1/2 was demonstrated using monoclonal antibodies. DIM, isosafrole, beta-naphthoflavone, 3-methylcholanthrene and naringenin added in vitro inhibited EH strongly in induced microsomes but gestodene was a better inhibitor of estrogen 2-hydroxylation in liver microsomes from untreated female rats. The binding affinities of 13C and DIM to the Ah receptor were compared to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by competition studies, and the IC50 values were shown to be 2.0 x 10(-9) M, 5.0 x 10(-5) M and 2.3 x 10(-3) M for TCDD, DIM and 13C, respectively. The ability of 13C or DIM to cause in vitro transformation of the Ah receptor to a form able to bind to the dioxin-responsive element-3 (DRE3) was compared to that of TCDD and shown to parallel their abilities to compete for binding of [3H]TCDD to the Ah receptor. These experiments confirm and extend the proposals that dietary indoles induce specific cytochrome P450s in rat liver by a mechanism possibly involving the Ah receptor. The induced monooxygenases, in turn, increase the synthesis of 2-hydroxylated estrogens in the competing pathways of 2- and 16 alpha-hydroxylation which decreases the levels of 16 alpha-hydroxyestrone able to form stable covalent adducts with proteins including the estrogen receptor. Such steroid-protein interaction has been correlated with mammary carcinogenesis.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3,3'-diindolylmethane,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/CYP2C11 protein, rat,
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/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Aryl Hydrocarbon,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug,
http://linkedlifedata.com/resource/pubmed/chemical/Steroid 16-alpha-Hydroxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Steroid Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrachlorodibenzodioxin,
http://linkedlifedata.com/resource/pubmed/chemical/estrogen 2-hydroxylase,
http://linkedlifedata.com/resource/pubmed/chemical/indole-3-carbinol
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0006-2952
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
9
|
| pubmed:volume |
45
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1129-36
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8384853-Animals,
pubmed-meshheading:8384853-Antioxidants,
pubmed-meshheading:8384853-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:8384853-Base Sequence,
pubmed-meshheading:8384853-Cytochrome P-450 CYP1A1,
pubmed-meshheading:8384853-Cytochrome P-450 Enzyme System,
pubmed-meshheading:8384853-DNA,
pubmed-meshheading:8384853-Enzyme Induction,
pubmed-meshheading:8384853-Estradiol,
pubmed-meshheading:8384853-Female,
pubmed-meshheading:8384853-Hydroxylation,
pubmed-meshheading:8384853-Indoles,
pubmed-meshheading:8384853-Microsomes, Liver,
pubmed-meshheading:8384853-Molecular Sequence Data,
pubmed-meshheading:8384853-Rats,
pubmed-meshheading:8384853-Rats, Sprague-Dawley,
pubmed-meshheading:8384853-Receptors, Aryl Hydrocarbon,
pubmed-meshheading:8384853-Receptors, Drug,
pubmed-meshheading:8384853-Steroid 16-alpha-Hydroxylase,
pubmed-meshheading:8384853-Steroid Hydroxylases,
pubmed-meshheading:8384853-Tetrachlorodibenzodioxin
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation.
|
| pubmed:affiliation |
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|