title: Transplacental transfer of acrylamide and glycidamide are comparable to that of antipyrine in perfused human placenta.
abstract: Most drugs can penetrate the placenta but there are only a few studies on placental transfer of environmental toxic compounds. In this study, we used dual recirculating human placental perfusion to determine the transfer rate through the placenta of a neurotoxic and carcinogenic compound found in food, acrylamide and its genotoxic metabolite glycidamide. Putative acrylamide metabolism into glycidamide during the 4-h perfusions and acrylamide-derived DNA adducts in placental DNA after perfusions were also analyzed. Placentas were collected immediately after delivery and kept physiologically functional as confirmed by antipyrine kinetics, glucose consumption and leak from fetal to maternal circulation. Acrylamide (5 or 10 microg/ml) or glycidamide (5 microg/ml), both with antipyrine (100 microg/ml), was added to maternal circulation. Acrylamide and glycidamide were analyzed in the perfusion medium by liquid chromatography/mass spectrometry. Acrylamide and glycidamide crossed the placenta from maternal to fetal circulation with similar kinetics to antipyrine, suggesting fetal exposure if the mother is exposed. The concentrations in maternal and fetal circulations equilibrated within 2h for both studied compounds and with both concentrations. Acrylamide metabolism into glycidamide was not detected during the 4-h perfusions. Moreover, DNA adducts were undetectable in the placentas after perfusions. However, fetuses may be exposed to glycidamide after maternal metabolism. Although not found in placental tissue after 4h of perfusion, it is possible that glycidamide adducts are formed in fetal DNA.
authors.affiliation: Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Annola
authors.forename: Vesa
authors.initials: V
authors.lastname: Karttunen
authors.forename: Pekka
authors.initials: P
authors.lastname: Keski-Rahkonen
authors.forename: Päivi
authors.initials: P
authors.lastname: Myllynen
authors.forename: Dan
authors.initials: D
authors.lastname: Segerbäck
authors.forename: Seppo
authors.initials: S
authors.lastname: Heinonen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vähäkangas
mesh_terms: D000178:Acrylamides / Q000378:metabolism*; D000328:Adult; D000983:Antipyrine / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D004852:Epoxy Compounds / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D008431:Maternal-Fetal Exchange / Q000502:physiology; D008970:Molecular Weight; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000178:Acrylamides; D004852:Epoxy Compounds; C071834:glycidamide; D004247:DNA; D000983:Antipyrine