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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1997-9-11
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pubmed:abstractText |
We examined the potential for the widely consumed xenobiotic ethanol to transplacentally induce fetal rat CYP2E1. Throughout gestation, rat dams were fed a liquid diet containing 5% ethanol or two separate control diets. At 2 days before term, the dams were killed, and maternal and embryonic tissues were collected. Immunoblot analysis of microsomes from fetal liver, placenta and maternal brain revealed a band that comigrated with adult liver CYP2E1. The identity of the immunoreactive protein in placenta, brain and fetal liver was substantiated as CYP2E1 through restriction enzyme digestion of a reverse transcription-polymerase chain reaction product. Quantification of immunoblots containing microsomes from maternal and fetal liver of ethanol-treated dams displayed a 1.4- and 2.4-fold increase in CYP2E1, respectively, compared with microsomes from pair-fed controls. Chlorzoxazone and low substrate concentrations of N-nitrosodimethylamine were used as metabolic probes for CYP2E1. The rate of chlorzoxazone metabolism by maternal hepatic microsomes from dams fed the 5% ethanol diet was 2.6-fold greater than that of controls. Conversely, a negligible increase was observed in the rate of metabolism by hepatic microsomes from ethanol-exposed fetuses compared with pair-fed animals. When N-nitrosodimethylamine demethylation was examined, these same fetal samples exhibited greater rates of activity (1.5-fold) compared with microsomes from control animals. However, this increase was not as great as expected considering the 2.4-fold increase in CYP2E1 protein. Collectively, fetuses exposed to a 5% ethanol diet throughout gestation exhibited transplacental induction of an hepatic CYP2E1 that may possess different catalytic properties from the analogous adult enzyme.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-nitrosodimethylaniline,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorzoxazone,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP2E1,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanol,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroso Compounds
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1028-36
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9262372-Animals,
pubmed-meshheading:9262372-Catalysis,
pubmed-meshheading:9262372-Chlorzoxazone,
pubmed-meshheading:9262372-Cytochrome P-450 CYP2E1,
pubmed-meshheading:9262372-Enzyme Induction,
pubmed-meshheading:9262372-Ethanol,
pubmed-meshheading:9262372-Female,
pubmed-meshheading:9262372-Fetus,
pubmed-meshheading:9262372-Immunohistochemistry,
pubmed-meshheading:9262372-Microsomes, Liver,
pubmed-meshheading:9262372-Nitroso Compounds,
pubmed-meshheading:9262372-Placenta,
pubmed-meshheading:9262372-Pregnancy,
pubmed-meshheading:9262372-Rats
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pubmed:year |
1997
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pubmed:articleTitle |
Ethanol-mediated transplacental induction of CYP2E1 in fetal rat liver.
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pubmed:affiliation |
University of New Mexico, College of Pharmacy, Albuquerque, USA. scarpen@agi.org
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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