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rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
2002-11-27
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pubmed:abstractText |
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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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-10357718,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-10485464,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-10493507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-10722106,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-10825126,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-11016657,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-11036110,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-11202048,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-11463829,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-11497241,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-11533706,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-11590207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-11956086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-12045106,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-12089223,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-12218177,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-12477054,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-12477055,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-2404325,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-4437147,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-4820970,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-6735553,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-8031966,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-8607854,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-8899027,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429862-9624113
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pubmed:language |
eng
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ABCG2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorophyll,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Photosensitizing Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Porphyrins,
http://linkedlifedata.com/resource/pubmed/chemical/Protoporphyrins,
http://linkedlifedata.com/resource/pubmed/chemical/Topotecan,
http://linkedlifedata.com/resource/pubmed/chemical/pheophorbide a,
http://linkedlifedata.com/resource/pubmed/chemical/protoporphyrin IX
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pubmed:status |
MEDLINE
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pubmed:author |
pubmed-author:BeijnenJos HJH,
pubmed-author:BuitelaarMarijeM,
pubmed-author:ElferinkRonald P J OudeRP,
pubmed-author:JonkerJohan WJW,
pubmed-author:KuipersFolkertF,
pubmed-author:PloschTorstenT,
pubmed-author:RosingHildeH,
pubmed-author:SchefferGeorge LGL,
pubmed-author:ScheperRik JRJ,
pubmed-author:SchinkelAlfred HAH,
pubmed-author:Van Der ValkMartin AMA,
pubmed-author:WagenaarElsE
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15649-54
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pubmed:dateRevised |
2009-11-18
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pubmed:articleTitle |
The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria.
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pubmed:affiliation |
Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
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