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

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-blpyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of C-14-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 K0143 increased the transfer of C-14-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 C-14-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 C-14-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarinorna cells. (C) 2008 Elsevier Inc. All rights reserved.