ToxSci Advance Access published online on October 29, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp257
Aflatoxin B1 transfer and metabolism in human placenta
1 Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland 2 University of Hong Kong, School of Biological Sciences, S5-13 Kadoorie Biological Sciences Building Pokfulam, Hong Kong, SAR China 3 Department of Pharmaceutical Chemistry, University of Kuopio, P.O.Box 1627, FIN-70211 Kuopio, Finland 4 Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, P.O.Box 5000, 90014 Oulu, Finland
Corresponding author: Kirsi Vähäkangas, Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland, E-Mail: Kirsi.Vahakangas{at}uku.fi, Phone: +358 40 745 5254, Fax: +358 17 16 2424
Received July 3, 2009; revision received September 24, 2009; accepted October 12, 2009
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Abstract |
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Aflatoxin B1 (AFB1), a common dietary contaminant, is a major risk factor of hepatocellular carcinoma (HCC). Early onset of HCC in some countries in Africa and South-East Asia indicates the importance of early life exposure. Placenta is the primary route for various compounds, both nutrients and toxins, from the mother to the fetal circulation. Furthermore, placenta contains enzymes for xenobiotic metabolism. AFB1, AFB1-metabolites and AFB1-albumin adducts have been detected in cord blood of babies after maternal exposure during pregnancy. However, the role that the placenta plays in the transfer and metabolism of AFB1 is not clear. In this study, placental transfer and metabolism of AFB1 were investigated in human placental perfusions and in in vitro studies. Eight human placentas were perfused with 0.5 or 5 µM AFB1 for 2-4 hours. In vitro incubations with placental microsomal and cytosolic proteins from eight additional placentas were also conducted. Our results from placental perfusions provide the first direct evidence of the actual transfer of AFB1 and its metabolism to aflatoxicol (AFL) by human placenta. In vitro incubations with placental cytosolic fraction confirmed the capacity of human placenta to form AFL. AFL was the only metabolite detected in both perfusions and in vitro incubations. Since AFL is less mutagenic, but putatively as carcinogenic as AFB1, the formation of AFL may not protect the fetus from the toxicity of AFB1.
Key Words: Human placental perfusion; fetal exposure; placental cytosolic fraction; aflatoxicol; dietary carcinogen.