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

Expression of the Ah receptor-regulated cytochrome P4501B1 (CYP1B1) ge ne was studied in human adult and fetal tissues and cells in culture b y reverse transcriptase-coupled polymerase chain reaction (RT-PCR), In adults, CYP1B1 mRNA was detected in liver, lymphocytes, cells of bron choalveolar lavage samples and uterine endometrium, but not in lung, T he level of expression was very low in adult liver and only three out of six fetal livers expressed CYP1B1, Extrahepatic fetal tissues, espe cially brains and kidneys, expressed high levels of CYP1B1, CYP1B1 mRN A was constitutively detected at a low level in first trimester and fu ll-term placental samples, A competitive RT-PCR assay was developed to assess the regulation of CYP1B1, CYP1B1 mRNA was not induced in place nta 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 CYP1B 1 was found to be regulated independently from CYP1A1, In JEG-3 cells CYP1A1 mRNA was induced up to 9000-fold, while the expression of CYP1B I was not affected, Expression of Ah receptor and Ah receptor nuclear translocator (regulators of the CYP1 family) was determined in human p lacenta and in the JEG-3 cell line, Expression of these transcription factors was found neither to be co-regulated nor affected by Ah recept or ligands, This study provides evidence that in addition to the Ah re ceptor complex, other cell-specific factors modulate the response of C YP1B1 and CYP1A1 to Ah receptor ligands.