Aflatoxin B1 transfer and metabolism in human placenta.
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 5microM AFB1 for 2-4 h. 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.
Partanen
Heidi A
HA
Department of Pharmacology and Toxicology, University of Kuopio, FIN-70211 Kuopio, Finland.
El-Nezami
Hani S
HS
Leppänen
Jukka M
JM
Myllynen
Päivi K
PK
Woodhouse
Heather J
HJ
Vähäkangas
Kirsi H
KH
D016604:Aflatoxin B1 / Q000378:metabolism*; D000348:Aflatoxins / Q000378:metabolism*; D001692:Biological Transport; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008431:Maternal-Fetal Exchange; D008861:Microsomes / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy
D000348:Aflatoxins; D009153:Mutagens; C012170:aflatoxicol; D004247:DNA; D016604:Aflatoxin B1