finrozole and Choriocarcinoma

Previous studies have indicated that aromatase (CYP19A1) is involved in the metabolism of aflatoxin B1 (AFB1). We hypothesized that exposure to AFB1 contaminated food during pregnancy could disrupt the normal production of steroid hormones in placenta. We examined the capability of AFB1 exposure to disrupt CYP19A1 expression as a putative endocrine disrupter, and to investigate the metabolism of AFB1 by CYP19A1. JEG-3 cells, as model for placental cells, were exposed alone and in combination to AFB1 and estrogen receptor ligands for 24-96 h. AFB1 (0.3-1.0 μM) induced the expression of CYP19A1 by 163%-339% compared to control at the 96 h time point, although no induction was observed at 24 h. AFB1 concentrations higher than 1 μM were cytotoxic to JEG-3 cells, and the cytotoxicity was inhibited by the aromatase inhibitor, finrozole. AFB1 was metabolized to aflatoxicol (AFL) by JEG-3 cells and CYP19A1 recombinant protein. AFL formation was partially inhibited by addition of tamoxifen and finrozole to the JEG-3 cells. AFB1 had no effect on the expression of CYP1A2 and CYP3A4 in JEG-3 cells. These results reveal that AFB1 can affect the expression of aromatase enzyme, indicating that chronic exposure to AFB1 may cause endocrine disruption in the foetoplacental unit.

Topics: Aflatoxin B1; Aflatoxins; Aromatase; Aromatase Inhibitors; Cell Line, Tumor; Choriocarcinoma; Cytochrome P-450 CYP1A1; Drug Combinations; Endocrine Disruptors; Female; Gene Expression Regulation, Enzymologic; Humans; Nitriles; Poisons; Recombinant Proteins; Tamoxifen; Triazoles; Trophoblasts; Up-Regulation