Expression of xenobiotic-metabolizing cytochrome P450 forms in human full-term placenta

被引:172
|
作者
Hakkola, J
Pasanen, M
Hukkanen, J
Pelkonen, O
Maenpaa, J
Edwards, RJ
Boobis, AR
Raunio, H
机构
[1] UNIV KUOPIO, DEPT PHARMACOL & TOXICOL, SF-90721 KUOPIO, FINLAND
[2] ROYAL POSTGRAD MED SCH, DEPT CLIN PHARMACOL, LONDON W12 0NN, ENGLAND
关键词
cytochrome P450; maternal-fetal exchange; smoking; polymerase chain reaction;
D O I
10.1016/0006-2952(95)02184-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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, CYP2E1, CYP2F1, CYP3A3/4, CYP3A5, and CYP4B1 were detected by RT-PCR, and CYP1A2, CYP2A6/7, CYP2B6/7, CYP2C8-19, CYP2D6, and CYP3A7 were not detected. Several enzyme activity assays and immunoblots were used to further characterize expression of forms producing detectable mRNA transcripts. The catalytic activities of 7-ethoxycoumarin O-deethylase (ECOD), 7-ethoxyresorufin O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH) were substantially increased in response to maternal cigarette smoking, and paralleled the amount of CYP1A1 mRNA and protein. Aromatase activities were slightly lower in placentas exposed to cigarette smoke compared with nonexposed placentas. These data show that several xenobiotic-metabolizing CYP genes are expressed in human placenta at a low level. The significance of such low-level expression is unknown, but it may have local physiological or toxic consequences.
引用
收藏
页码:403 / 411
页数:9
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