Carcinogenesis, Vol 18, 391-397, Copyright © 1997 by Oxford University Press
J Hakkola, M Pasanen, O Pelkonen, J Hukkanen, S Evisalmi, S Anttila, A Rane, M Mantyla, R Purkunen, S Saarikoski, M Tooming and H Raunio
Expression of the Ah receptor-regulated cytochrome P4501B1 (CYP1B1) gene
was studied in human adult and fetal tissues and cells in culture by
reverse transcriptase-coupled polymerase chain reaction (RT-PCR). In
adults, CYP1B1 mRNA was detected in liver, lymphocytes, cells of
bronchoalveolar lavage samples and uterine endometrium, but not in lung.
The level of expression was very low in adult liver and only three out of
six fetal livers expressed CYP1B1. Extrahepatic fetal tissues, especially
brains and kidneys, expressed high levels of CYP1B1. CYP1B1 mRNA was
constitutively detected at a low level in first trimester and full-term
placental samples. A competitive RT-PCR assay was developed to assess the
regulation of CYP1B1. CYP1B1 mRNA was not induced in placenta by maternal
cigarette smoking. Inducibility of CYP1B1 in cells in culture by the Ah
receptor ligand 2,3,7,8- tetrachlorodibenzo-p-dioxin was studied in primary
fibroblasts and chorion carcinoma cell line JEG-3 having different CYP1A1
induction properties. Inducibility of CYP1B1 was found to be regulated
independently from CYP1A1. In JEG-3 cells CYP1A1 mRNA was induced up to
9000-fold, while the expression of CYP1B1 was not affected. Expression of
Ah receptor and Ah receptor nuclear translocator (regulators of the CYP1
family) was determined in human placenta and in the JEG-3 cell line.
Expression of these transcription factors was found neither to be
co-regulated nor affected by Ah receptor ligands. This study provides
evidence that in addition to the Ah receptor complex, other cell- specific
factors modulate the response of CYP1B1 and CYP1A1 to Ah receptor ligands.
ARTICLES
Expression of CYP1B1 in human adult and fetal tissues and differential inducibility of CYP1B1 and CYP1A1 by Ah receptor ligands in human placenta and cultured cells
Department of Pharmacology and Toxicology, University of Oulu, Finland.
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