The presence of inducible cytochrome P450 types 1A1 and 1A2 in the BeWo cell line.
The activity and inducibility of cytochrome P450 systems (CYP1A1:1A2) of the human placenta were assessed in a representative human trophoblast-like cell line, BeWo. The activity of CYP1A1 and CYP1A2 in microsome preparations from human liver, placenta, primary cultures of human cytotrophoblast, and BeWo cells was measured by O -dealkylation of 7-ethoxyresorufin (EROD) and 7-methoxyresorufin O -demethylation (MROD), respectively. Results indicated high EROD and MROD activity associated with human liver microsomes, sometimes comparable activities in human placenta microsomes prepared from smokers, and relatively low activities in human placenta microsomes from nonsmokers and in the primary cultures of cytotrophoblasts isolated from nonsmokers. Microsomes from BeWo cell monolayers exhibited the lowest EROD and MROD activities relative to all other microsome preparations. However, compared to primary cultures of normal trophoblasts, the EROD activity of the BeWo cells was far more sensitive to typical inducers, 3-methylcholanthrene, 1,2-benzanthracene, and beta-naphthoflavone. EROD activity in BeWo cells was induced approximately 200-fold by 3-methylcholanthrene. Both EROD and MROD activity in BeWo cells was readily induced by 1,2-benzanthracene, 100-fold and 60-fold, respectively. After induction with 1,2-benzanthracene, the CYP1A1 selective inhibitor, alpha-naphthoflavone, and the CYP1A2 selective inhibitor, furafylline, effectively inhibited enzyme activities with IC(50)s of 2.4 microM and 12.8 microM, respectively, in microsomes from both trophoblasts culture systems. These results show that major cytochrome P450 forms present in human placenta are present and inducible in BeWo cells, a potential model for investigation of drug metabolism mechanisms in the human trophoblast.
Avery
M L
ML
Department of Pharmaceutical Chemistry, School of Pharmacy, The University of Kansas, Lawrence 66047, USA.
Meek
C E
CE
Audus
K L
KL
D001551:Benz(a)Anthracenes / Q000494:pharmacology; D001571:Benzoflavones / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D012907:Smoking; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014327:Trophoblasts / Q000187:drug effects / Q000201:enzymology*; D014407:Tumor Cells, Cultured; D019324:beta-Naphthoflavone / Q000494:pharmacology
D001551:Benz(a)Anthracenes; D001571:Benzoflavones; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004791:Enzyme Inhibitors; D008748:Methylcholanthrene; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone; D013806:Theophylline; C050131:furafylline; C030935:benz(a)anthracene; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2