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Toxicology Letters
Article . 2011 . Peer-reviewed
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Article . 2011
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Aflatoxin B1 – a potential endocrine disruptor – up-regulates CYP19A1 in JEG-3 cells

Authors: ElNezami, H; Huuskonen, P; Storvik, M; Auriola, S; Lehtonen, S; Pasanen, M; Kyllönen, T;

Aflatoxin B1 – a potential endocrine disruptor – up-regulates CYP19A1 in JEG-3 cells

Abstract

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.

Country
China (People's Republic of)
Related Organizations
Keywords

570, Aflatoxin B1, Placenta, JEG-3, Endocrine Disruptors, Gene Expression Regulation, Enzymologic, Poisons, Aromatase, Aflatoxins, Cell Line, Tumor, Nitriles, Cytochrome P-450 CYP1A1, Humans, Choriocarcinoma, Aflatoxin B1 - metabolism - toxicity, Aromatase Inhibitors, Aromatase - genetics - metabolism, Triazoles, Poisons - metabolism - toxicity, Recombinant Proteins, Trophoblasts, Up-Regulation, Drug Combinations, Tamoxifen, Endocrine disruptor, Aflatoxicol, Endocrine Disruptors - toxicity, Female, Trophoblasts - drug effects - enzymology - pathology

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    popularity
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    Top 10%
    influence
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
53
Top 10%
Top 10%
Top 10%