Expression of CYP2E1 during embryogenesis and fetogenesis in human cephalic tissues: implications for the fetal alcohol syndrome.
Reverse transcription and the polymerase chain reaction (RT-PCR) with oligonucleotide primers designed to target cDNA nucleotides 1241-1357 corresponding to exons 8 (3' end) and 9 (5' end) in human genomic CYP2E1 detected consistently strong signals in 9 of 10 prenatal human brains. Cephalic tissues analyzed were between 54 and 78 days of gestation. RT-PCR signals for expression of CYP2E1 in corresponding human hepatic or adrenal tissues were weaker or, with only 2 exceptions, undetectable. Attempts to approximate levels of P4502E1 mRNA with Northern blots and RNase protection assays indicated that levels in human prenatal whole brain tissues tended to increase as a function of gestational age but, at the early stages investigated, were far lower than the constitutive levels in hepatic tissues of adult humans or male rats. Localized, P4502E1-dependent cephalic bioactivation of ethanol, with associated generation of several reactive chemical species, could contribute significantly to the etiology of neuroembryotoxic effects of prenatal ethanol exposure.
Boutelet-Bochan
H
H
School of Medicine, University of Washington, Seattle, Washington 98195, USA.
Huang
Y
Y
Juchau
M R
MR
D000328:Adult; D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology*; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D063647:Fetal Alcohol Spectrum Disorders; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
D012333:RNA, Messenger; D019392:Cytochrome P-450 CYP2E1