The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk

Contamination of milk with drugs, pesticides and other xenotoxins can pose a major health risk to breast-fed infants and dairy consumers. Here we show that the multidrug transporter BCRP (encoded by ABCG2) is strongly induced in the mammary gland of mice, cows and humans during lactation and that it is responsible for the active secretion of clinically and toxicologically important substrates such as the dietary carcinogen PhIP, the anticancer drug topotecan and the antiulcerative cimetidine into mouse milk.

[1]  S. Bates,et al.  Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. , 2003, Cancer research.

[2]  Jos H Beijnen,et al.  The breast cancer resistance protein (Bcrp1/Abcg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. , 2003, Cancer research.

[3]  P. McNamara,et al.  Acyclovir, Ganciclovir, and Zidovudine Transfer into Rat Milk , 2002, Antimicrobial Agents and Chemotherapy.

[4]  P. McNamara,et al.  Active transport of cimetidine and ranitidine into the milk of Sprague Dawley rats. , 1996, The Journal of pharmacology and experimental therapeutics.

[5]  Å. Andreassen,et al.  Neonatal exposure to the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine via breast milk or directly induces intestinal tumors in multiple intestinal neoplasia mice. , 1999, Carcinogenesis.

[6]  Xin Wang,et al.  Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. , 2003, Molecular pharmacology.

[7]  M. Peaker,et al.  Transport of milk constituents by the mammary gland. , 2000, Physiological reviews.

[8]  Yuichi Sugiyama,et al.  ABCG2 Transports Sulfated Conjugates of Steroids and Xenobiotics* , 2003, Journal of Biological Chemistry.

[9]  Alfred H. Schinkel,et al.  Human Breast Cancer Resistance Protein: Interactions with Steroid Drugs, Hormones, the Dietary Carcinogen 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and Transport of Cimetidine , 2005, Journal of Pharmacology and Experimental Therapeutics.

[10]  H. Rosing,et al.  The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Y. Schneider,et al.  Chloroquine accumulates in breast-milk cells: potential impact in the prophylaxis of postnatal mother-to-child transmission of HIV-1. , 2001, AIDS.

[12]  L. Doyle,et al.  A multidrug resistance transporter from human MCF-7 breast cancer cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. Phillips,et al.  DNA damage in human breast milk cells and its induction by 'early' and 'late' milk extracts. , 2000, Carcinogenesis.