| The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. | |
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MedLine Citation:
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PMID: 12429862 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The breast cancer resistance protein (BCRPABCG2) is a member of the ATP-binding cassette family of drug transporters and confers resistance to various anticancer drugs. We show here that mice lacking Bcrp1Abcg2 become extremely sensitive to the dietary chlorophyll-breakdown product pheophorbide a, resulting in severe, sometimes lethal phototoxic lesions on light-exposed skin. Pheophorbide a occurs in various plant-derived foods and food supplements. Bcrp1 transports pheophorbide a and is highly efficient in limiting its uptake from ingested food. Bcrp1(-/-) mice also displayed a previously unknown type of protoporphyria. Erythrocyte levels of the heme precursor and phototoxin protoporphyrin IX, which is structurally related to pheophorbide a, were increased 10-fold. Transplantation with wild-type bone marrow cured the protoporphyria and reduced the phototoxin sensitivity of Bcrp1(-/-) mice. These results indicate that humans or animals with low or absent BCRP activity may be at increased risk for developing protoporphyria and diet-dependent phototoxicity and provide a striking illustration of the importance of drug transporters in protection from toxicity of normal food constituents. |
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Authors:
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Johan W Jonker; Marije Buitelaar; Els Wagenaar; Martin A Van Der Valk; George L Scheffer; Rik J Scheper; Torsten Plosch; Folkert Kuipers; Ronald P J Oude Elferink; Hilde Rosing; Jos H Beijnen; Alfred H Schinkel |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2002-11-12 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 99 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2002 Nov |
Date Detail:
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Created Date: 2002-11-27 Completed Date: 2003-01-14 Revised Date: 2013-04-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 15649-54 Citation Subset: IM |
Affiliation:
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Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics,
physiology* Administration, Oral Animals Bone Marrow Transplantation Cell Line Chlorophyll / administration & dosage, analogs & derivatives*, pharmacokinetics, toxicity* Chromatography, High Pressure Liquid Dermatitis, Phototoxic / etiology, prevention & control* Diet / adverse effects Drug Resistance / genetics* Female Fetus / metabolism Fibroblasts / metabolism Genetic Predisposition to Disease Medicago sativa / adverse effects Mice Mice, Inbred Strains Mice, Knockout Molecular Structure Neoplasm Proteins* Photosensitizing Agents / administration & dosage, pharmacokinetics, toxicity* Porphyria, Hepatoerythropoietic / genetics, prevention & control*, therapy Porphyrins / metabolism*, pharmacokinetics Pregnancy Protoporphyrins / blood*, chemistry Radiation Chimera Topotecan / pharmacokinetics, toxicity |
| Chemical | |
Reg. No./Substance:
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0/ABCG2 protein, human; 0/Neoplasm Proteins; 0/Photosensitizing Agents; 0/Porphyrins; 0/Protoporphyrins; 123948-87-8/Topotecan; 1406-65-1/Chlorophyll; 15664-29-6/pheophorbide a; 553-12-8/protoporphyrin IX |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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