EXPRESSION OF CYP2E1 DURING EMBRYOGENESIS AND FETOGENESIS IN HUMAN CEPHALIC TISSUES - IMPLICATIONS FOR THE FETAL ALCOHOL SYNDROME

Reverse transcription and the polymerase chain re action (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 CYP 2E1 detected consistently strong signals in 9 of 10 prenatal human bra ins. Cephalic tissues analyzed were between 54 and 78 days of gestatio n. RT-PCR signals for expression of CYP2E1 in corresponding human hepa tic or adrenal tissues were weaker or, with only 2 exceptions, undetec table, Attempts to approximate levels of P4502E1 mRNA with Northern bl ots and RNase protection assays indicated that levels in human prenata l whole brain tissues tended to increase as a function of gestational age but, at the early stages investigated, were far lower than the con stitutive levels in hepatic tissues of adult humans or male rats. Loca lized, P4502E1-dependent cephalic bioactivation of ethanol, with assoc iated generation of several reactive chemical species, could contribut e significantly to the etiology of neuroembryotoxic effects of prenata l ethanol exposure. (C) 1997 Academic Press.