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.
Copyright 1997 Academic Press.