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

Abstract

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.

Cytochrome P450 Cyp1b1*2 Gene and Its Association With T2d in Tabuk Population, Northwestern Region of Saudi Arabia

“…The crystal structure of the CYP1B1 was determined [7], it has a narrow slot-like active site that is similar to that of CYP1A1; however, the residues around the edge of the active sites are different for specific binding of substrates and inhibitors [7]. Using the reverse transcriptase-coupled polymerase chain reaction (RT-PCR), CYP1B1 mRNA was detected in hepatocytes, lymphocytes, and uterus [8]. CYP1B1 gene is expressed in different amount among tissues, the highest mRNA expression levels were found in extrahepatic tissues such as renal, uterine, heart, brain, lung, and skeletal muscle [9].…”

Human CYP1B1 Is Regulated by Estradiol via Estrogen Receptor

“…9 -11). Of particular interest is the fact that CYP1B1 is highly expressed in estrogen-related tissues such as mammary, uterus, and ovary (4,12), suggesting that CYP1B1 is important in the localized metabolic control of estrogen homeostasis. 4-Hydroxyestradiol, a catechol metabolite formed by CYP1B1 from E2, leads to decrease of the estrogenic activity.…”

Tumor-selective drug activation: a GDEPT approach utilizing cytochrome P450 1A1 and AQ4N

“…However, no information was given as to whether the polyclonal antibody used was raised against CYP1A1 or 1A2 isoforms. In addition, since CYP1A1 is primarily located in extra-hepatic tissues, such as lung, lymphocytes and placenta, [27][28][29][30][31][32] it is unlikely to have been present in the liver microsomal fractions used by Raleigh et al This is the first report suggesting that CYP1A1 can metabolise AQ4N and since CYP1A1 expression is high in various types of ovarian cancers compared with benign epithelia, 33 our data suggest that targeting these tumor types in combination with oxic cell killers, such as radiation or chemotherapy, even in the absence of a GDEPT approach, may be beneficial.…”