
To characterize transplacental transfer of melamine and related mechanisms as well as toxicity using human placental perfusion and cultured cells.Transfer and toxicity were analyzed in 4-h perfusions with 10 μM or 1 mM melamine, or 10 μM melamine with 10 nM cyanuric acid (CYA). Efflux transporters were studied in accumulation assay and toxicity in BeWo cells by MTT assay.Of added melamine 34-45% was transferred to fetal circulation and CYA made no difference. Histology, hCG production, and PLAP activity indicated functionality of placental tissue with no grave toxicity. Highest concentration of melamine used (2 mM) with CYA and long treatment time decreased viability of BeWo cells. Inhibitors of ABCB1, ABCG2, ABCC2 did not affect the accumulation of melamine in cells.Melamine goes through human term placenta with no contribution of efflux transporters. Toxicity of melamine is low in placental tissue and BeWo cells.
ATP-Binding Cassette, Sub-Family C Proteins, ATP Binding Cassette Transporter, Subfamily B, Cell Survival - drug effects, Placenta - blood supply - cytology - drug effects - physiology, Cell Survival, Placenta, Perfusion - methods, P-Glycoprotein - antagonists & inhibitors, In Vitro Techniques, Chorionic Gonadotropin, Chorionic Gonadotropin - secretion, Cell Line, ATP-Binding Cassette Transporters - antagonists & inhibitors, Pregnancy, Triazines - metabolism - pharmacology - toxicity, Membrane Transport Modulators, Resins, Synthetic - metabolism - toxicity, Synthetic - metabolism - toxicity, ATP Binding Cassette Transporter, Subfamily G, Member 2, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, Membrane Transport Modulators - pharmacology, Maternal-Fetal Exchange, Maternal-Fetal Exchange - drug effects, Neoplasm Proteins - antagonists & inhibitors, Pregnancy Proteins - antagonists & inhibitors - metabolism - secretion, Biological Transport, Trophoblasts - cytology - drug effects - metabolism, Biological Transport - drug effects, Multidrug Resistance-Associated Protein 2, Neoplasm Proteins, Perfusion, Kinetics, Multidrug Resistance-Associated Proteins - antagonists & inhibitors, ATP-Binding Cassette Transporters, Female, Resins
ATP-Binding Cassette, Sub-Family C Proteins, ATP Binding Cassette Transporter, Subfamily B, Cell Survival - drug effects, Placenta - blood supply - cytology - drug effects - physiology, Cell Survival, Placenta, Perfusion - methods, P-Glycoprotein - antagonists & inhibitors, In Vitro Techniques, Chorionic Gonadotropin, Chorionic Gonadotropin - secretion, Cell Line, ATP-Binding Cassette Transporters - antagonists & inhibitors, Pregnancy, Triazines - metabolism - pharmacology - toxicity, Membrane Transport Modulators, Resins, Synthetic - metabolism - toxicity, Synthetic - metabolism - toxicity, ATP Binding Cassette Transporter, Subfamily G, Member 2, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, Membrane Transport Modulators - pharmacology, Maternal-Fetal Exchange, Maternal-Fetal Exchange - drug effects, Neoplasm Proteins - antagonists & inhibitors, Pregnancy Proteins - antagonists & inhibitors - metabolism - secretion, Biological Transport, Trophoblasts - cytology - drug effects - metabolism, Biological Transport - drug effects, Multidrug Resistance-Associated Protein 2, Neoplasm Proteins, Perfusion, Kinetics, Multidrug Resistance-Associated Proteins - antagonists & inhibitors, ATP-Binding Cassette Transporters, Female, Resins
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