title: Placental transfer and DNA binding of benzo(a)pyrene in human placental perfusion.
abstract: Benzo(a)pyrene (BP) is the best studied polycyclic aromatic hydrocarbon, classified as carcinogenic to humans. The carcinogenic metabolite, benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), binds covalently to DNA. The key enzyme in this metabolic reaction is CYP1A1, which has also been found in placenta and human trophoblastic cells. By using human placental perfusion we confirmed that BP added to the maternal circulation in concentrations of 0.1 and 1 microM reaches fetal compartment but somewhat slower than the freely diffusible reference substance antipyrine. A well-known P-glycoprotein (ABCB1/P-gp) antagonist verapamil did not affect the transfer more than it did in the case of antipyrine, indicating that ABCB1/P-gp does not have a role in BP transfer. In one of the two placentas perfused for 6 h with the higher concentration of BP (1 microM) BPDE specific DNA adducts were found in placental tissue after the perfusion, but not before. The ability of human trophoblastic cells to activate BP to BPDE-DNA adducts was confirmed in human trophoblastic BeWo cells. This study shows that maternal exposure to BP leads to the exposure of the fetus to BP and/or its metabolites and that placenta itself can activate BP to DNA adducts.
authors.affiliation: Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Vesa
authors.initials: V
authors.lastname: Karttunen
authors.forename: Päivi
authors.initials: P
authors.lastname: Myllynen
authors.forename: Gabriela
authors.initials: G
authors.lastname: Prochazka
authors.forename: Olavi
authors.initials: O
authors.lastname: Pelkonen
authors.forename: Dan
authors.initials: D
authors.lastname: Segerbäck
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vähäkangas
mesh_terms: D001564:Benzo(a)pyrene / Q000737:chemistry*; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D010477:Perfusion; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D011247:Pregnancy; D013997:Time Factors
chemical_list: D018736:DNA Adducts; D001564:Benzo(a)pyrene; D004247:DNA; D019363:Cytochrome P-450 CYP1A1