title: The effects of aflatoxin B1 on transporters and steroid metabolizing enzymes in JEG-3 cells.
abstract: Effects of 96 h aflatoxin B1 (AFB1) exposure at concentrations from 0.2 μM to 6 μM on the mRNA and protein expression levels of the following transporters ABCB1/B4, ABCC1, ABCC2, ABCG2, OAT4 and the mRNA expression of steroid-metabolizing enzymes CYP1A1, CYP19A1, HSD3B1 and HSD17B1, and conjugating enzyme family UGT1A were evaluated in trophoblastic JEG-3 cells. Statistically significant dose-dependent five-fold increases in the expression levels with ABCC2 and OAT4 were recorded at 2 and 6μM AFB1. Protein expression of ABCG2 was decreased dose-dependently with 0.2-6 μM AFB1. With the other transporters, only a trend of increased expression was observed. Analogously, a three-fold increase in the expressions of CYP19A1, HSD3B1, HSD17B1 and UGT1A-family were observed at 0.3 μM AFB1. When an inhibitor of CYP19A1, finrozole, was dosed simultaneously with AFB1, no increases in the transcripts of transporters or steroid hydroxylases or CYP19A1 were observed. This delayed increase in the expression levels - only after 96h incubations - may indicate that the response is due to a secondary metabolite of AFB1 or other secondary controlling cascades rather than the parent compound itself. In conclusion, AFB1 affected the placental steroid synthesizing, metabolizing and conjugating enzymes as well as the expression levels of several transporter proteins in JEG-3 cells. These alterations may lead to anomalies in the foetoplacental hormonal homeostasis.
authors: University of Eastern Finland, Faculty of Health Sciences, School of Pharmacy, FI-70211 Kuopio, Finland. pasi.huuskonen@uef.fi
authors: Pasi
authors: P
authors: Huuskonen
authors: Päivi
authors: P
authors: Myllynen
authors: Markus
authors: M
authors: Storvik
authors: Markku
authors: M
authors: Pasanen
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016604:Aflatoxin B1 / Q000494:pharmacology*; D001141:Aromatase / Q000378:metabolism; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000201:enzymology* / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D004960:Estradiol Dehydrogenases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000187:drug effects / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011375:Progesterone Reductase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013251:Steroid Isomerases / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D013997:Time Factors
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D016604:Aflatoxin B1; D001141:Aromatase; D019363:Cytochrome P-450 CYP1A1; D004798:Enzymes; D004960:Estradiol Dehydrogenases; D014453:Glucuronosyltransferase; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D029362:Organic Anion Transporters, Sodium-Independent; D011375:Progesterone Reductase; D012333:RNA, Messenger; D013251:Steroid Isomerases; D013256:Steroids; C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C427207:SLC22A11 protein, human; C095122:multidrug resistance protein 3; C513331:HSD17B1 protein, human; C561410:CYP19A1 protein, human; C569463:CYP1A1 protein, human