title: Acute effects of ethanol on the transfer of nicotine and two dietary carcinogens in human placental perfusion.
abstract: Many mothers use, against instructions, alcohol during pregnancy. Simultaneously mothers are exposed to a wide range of other environmental chemicals. These chemicals may also harm the developing fetus, because almost all toxic compounds can go through human placenta. Toxicokinetic effects of ethanol on the transfer of other environmental compounds through human placenta have not been studied before. It is known that ethanol has lytic properties and increases the permeability and fluidity of cell membranes. We studied the effects of ethanol on the transfer of three different environmental toxins: nicotine, PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine) and NDMA (N-nitrosodimethylamine) in placental perfusion. We tested in human breast cancer adenocarcinoma cell line MCF-7 whether ethanol affects ABCG2/BCRP, which is also the major transporter in human placenta. We found that the transfer of ethanol is comparable to that of antipyrine, which points to passive diffusion as the transfer mechanism. Unexpectedly, ethanol had no statistically significant effect on the transfer of the other studied compounds. Neither did ethanol inhibit the function of ABCG2/BCRP. These experiments represent only the effects of acute exposure to ethanol and chronic exposure remains to be studied.
authors.affiliation: Faculty of Health Sciences, School of Pharmacy/Toxicology, University of Eastern Finland, P.O. BOX 1627, FI-70211 Kuopio, Finland.
authors.forename: Jenni
authors.initials: J
authors.lastname: Veid
authors.forename: Vesa
authors.initials: V
authors.lastname: Karttunen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Myöhänen
authors.forename: Päivi
authors.initials: P
authors.lastname: Myllynen
authors.forename: Seppo
authors.initials: S
authors.lastname: Auriola
authors.forename: Toivo
authors.initials: T
authors.lastname: Halonen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vähäkangas
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism; D000983:Antipyrine / Q000737:chemistry; D001692:Biological Transport / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D004058:Diffusion; D004128:Dimethylnitrosamine / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005506:Food Contamination; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D066298:In Vitro Techniques; D007202:Indicators and Reagents / Q000737:chemistry; D007700:Kinetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009538:Nicotine / Q000737:chemistry / Q000378:metabolism*; D010477:Perfusion; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D002250:Carbon Radioisotopes; D002273:Carcinogens; D007093:Imidazoles; D007202:Indicators and Reagents; D009363:Neoplasm Proteins; D000431:Ethanol; D009538:Nicotine; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D004128:Dimethylnitrosamine; D000983:Antipyrine