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

Journal Article · Wed Oct 15 00:00:00 EDT 2008 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2008.07.006· OSTI ID:21144137

Myllynen, Paeivi ^[1]; Kummu, Maria; Kangas, Tiina ^[1]; Ilves, Mika ^[2]; Immonen, Elina ^[1]; Rysae, Jaana; Pirilae, Rauna; Lastumaeki, Anni ^[1]; Vaehaekangas, Kirsi H ^[3]

---

1. Department of Pharmacology and Toxicology, University of Oulu, PO Box 5000, 90014, Oulu (Finland)
2. Department of Physiology, University of Oulu, PO Box 5000, 90014, Oulu (Finland)
3. Department of Pharmacology and Toxicology, University of Kuopio, PO Box 1627, 70211 Kuopio (Finland)

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.

• OSTI ID: 21144137
• Journal Information: Toxicology and Applied Pharmacology, Vol. 232, 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); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ATP
CARBON 14
CARCINOGENS
CONCENTRATION RATIO
FOOD
PERFUSED TISSUES
PLACENTA
PROTEINS
PYRIDINE