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Title: ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta

Abstract

We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of {sup 14}C-PhIP (2 {mu}M) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72 {+-} 0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of {sup 14}C-PhIP from maternal to fetal circulation (FM ratio 0.90 {+-} 0.08 at 6 h, p < 0.05) while the ABCC1/ABCC2 inhibitor probenecid had no effect (FM ratio at 6 h 0.75 {+-} 0.10, p = 0.84). There was a negative correlation between the expression of ABCG2 protein in perfused tissue and the FM ratio of {sup 14}C-PhIP (R = - 0.81, p < 0.01) at the end of the perfusion. The expression of ABCC2 protein did not correlate with FM ratio of PhIP (R: - 0.11, p = 0.76). In addition, PhIP induced the expression of ABC transporters in BeWo cells at mRNA level. In conclusion, our data indicates that ABCG2 decreases placental transfer of {sup 14}C-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarinoma cells.

Authors:
 [1]; ;  [2];  [3];  [2];  [4]; ; ;  [2];  [5]
  1. Department of Pharmacology and Toxicology, University of Oulu, PO Box 5000, 90014, Oulu (Finland), E-mail: paivi.myllynen@oulu.fi
  2. Department of Pharmacology and Toxicology, University of Oulu, PO Box 5000, 90014, Oulu (Finland)
  3. Department of Physiology, University of Oulu, PO Box 5000, 90014, Oulu (Finland)
  4. (Finland)
  5. Department of Pharmacology and Toxicology, University of Kuopio, PO Box 1627, 70211 Kuopio (Finland)
Publication Date:
OSTI Identifier:
21144137
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 232; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2008.07.006; PII: S0041-008X(08)00309-8; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ATP; CARBON 14; CARCINOGENS; CONCENTRATION RATIO; FOOD; PERFUSED TISSUES; PLACENTA; PROTEINS; PYRIDINE

Citation Formats

Myllynen, Paeivi, Kummu, Maria, Kangas, Tiina, Ilves, Mika, Immonen, Elina, Department of Pharmacology and Toxicology, University of Kuopio, PO Box 1627, 70211 Kuopio, Rysae, Jaana, Pirilae, Rauna, Lastumaeki, Anni, and Vaehaekangas, Kirsi H. ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta. United States: N. p., 2008. Web. doi:10.1016/j.taap.2008.07.006.
Myllynen, Paeivi, Kummu, Maria, Kangas, Tiina, Ilves, Mika, Immonen, Elina, Department of Pharmacology and Toxicology, University of Kuopio, PO Box 1627, 70211 Kuopio, Rysae, Jaana, Pirilae, Rauna, Lastumaeki, Anni, & Vaehaekangas, Kirsi H. ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta. United States. doi:10.1016/j.taap.2008.07.006.
Myllynen, Paeivi, Kummu, Maria, Kangas, Tiina, Ilves, Mika, Immonen, Elina, Department of Pharmacology and Toxicology, University of Kuopio, PO Box 1627, 70211 Kuopio, Rysae, Jaana, Pirilae, Rauna, Lastumaeki, Anni, and Vaehaekangas, Kirsi H. Wed . "ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta". United States. doi:10.1016/j.taap.2008.07.006.
@article{osti_21144137,
title = {ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta},
author = {Myllynen, Paeivi and Kummu, Maria and Kangas, Tiina and Ilves, Mika and Immonen, Elina and Department of Pharmacology and Toxicology, University of Kuopio, PO Box 1627, 70211 Kuopio and Rysae, Jaana and Pirilae, Rauna and Lastumaeki, Anni and Vaehaekangas, Kirsi H.},
abstractNote = {We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of {sup 14}C-PhIP (2 {mu}M) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72 {+-} 0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of {sup 14}C-PhIP from maternal to fetal circulation (FM ratio 0.90 {+-} 0.08 at 6 h, p < 0.05) while the ABCC1/ABCC2 inhibitor probenecid had no effect (FM ratio at 6 h 0.75 {+-} 0.10, p = 0.84). There was a negative correlation between the expression of ABCG2 protein in perfused tissue and the FM ratio of {sup 14}C-PhIP (R = - 0.81, p < 0.01) at the end of the perfusion. The expression of ABCC2 protein did not correlate with FM ratio of PhIP (R: - 0.11, p = 0.76). In addition, PhIP induced the expression of ABC transporters in BeWo cells at mRNA level. In conclusion, our data indicates that ABCG2 decreases placental transfer of {sup 14}C-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarinoma cells.},
doi = {10.1016/j.taap.2008.07.006},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 232,
place = {United States},
year = {Wed Oct 15 00:00:00 EDT 2008},
month = {Wed Oct 15 00:00:00 EDT 2008}
}