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pubmed-article:9262372pubmed:abstractTextWe 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.lld:pubmed
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pubmed-article:9262372pubmed:pagination1028-36lld:pubmed
pubmed-article:9262372pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:9262372pubmed:articleTitleEthanol-mediated transplacental induction of CYP2E1 in fetal rat liver.lld:pubmed
pubmed-article:9262372pubmed:affiliationUniversity of New Mexico, College of Pharmacy, Albuquerque, USA. scarpen@agi.orglld:pubmed
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pubmed-article:9262372pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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