EXPRESSION OF XENOBIOTIC-METABOLIZING CYTOCHROME-P450 FORMS IN HUMAN FULL-TERM PLACENTA

Citation
J. Hakkola et al., EXPRESSION OF XENOBIOTIC-METABOLIZING CYTOCHROME-P450 FORMS IN HUMAN FULL-TERM PLACENTA, Biochemical pharmacology, 51(4), 1996, pp. 403-411
Citations number
65
Categorie Soggetti
Pharmacology & Pharmacy",Biology
Journal title
ISSN journal
00062952
Volume
51
Issue
4
Year of publication
1996
Pages
403 - 411
Database
ISI
SICI code
0006-2952(1996)51:4<403:EOXCFI>2.0.ZU;2-5
Abstract
The expression of individual xenobiotic-metabolizing cytochrome P450 ( CYP) genes in human placenta was studied at the mRNA level by reverse transcriptase-polymerase chain reaction (RT-PCR). mRNAs of CYP1A1, CYP 2E1, CYP2F1, CYP3A3/4, CYP3A5, and CYP4B1 were detected by RT-PCR, and CYP1A2, CYP2A6/7, CYP2B6/7, CYP2C8-19, CYP2D6, and CYP3A7 were not de tected. Several enzyme activity assays and immunoblots were used to fu rther characterize expression of forms producing detectable mRNA trans cripts. The catalytic activities of 7-ethoxycoumarin O-deethylase (ECO D), 7-ethoxyresorufin O-deethylase (EROD) and aryl hydrocarbon hydroxy lase (AHH) were substantially increased in response to maternal cigare tte smoking, and paralleled the amount of CYP1A1 mRNA and protein. Aro matase activities were slightly lower in placentas exposed to cigarett e smoke compared with nonexposed placentas. These data show that sever al xenobiotic-metabolizing CYP genes are expressed in human placenta a t a low level. The significance of such low-level expression is unknow n, but it may have local physiological or toxic consequences.