Expression of xenobiotic-metabolizing cytochrome P450 forms in human full-term placenta.
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 immunoblasts 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 significant of such low-level expression is unknown, but it may have local physiological or toxic consequences.
Hakkola
J
J
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Pasanen
M
M
Hukkanen
J
J
Pelkonen
O
O
Mäenpää
J
J
Edwards
R J
RJ
Boobis
A R
AR
Raunio
H
H
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D001141:Aromatase / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001483:Base Sequence; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D017931:DNA Primers; D018076:DNA, Complementary; D005260:Female; D015870:Gene Expression; D006801:Humans; D008861:Microsomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D010088:Oxidoreductases / Q000378:metabolism; D010920:Placenta / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D012907:Smoking; D014158:Transcription, Genetic; D015262:Xenobiotics / Q000378:metabolism*
D017931:DNA Primers; D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D015660:7-Alkoxycoumarin O-Dealkylase; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A