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The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria.

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.

Pubmed ID: 12429862

Authors

  • Jonker JW
  • Buitelaar M
  • Wagenaar E
  • Van Der Valk MA
  • Scheffer GL
  • Scheper RJ
  • Plosch T
  • Kuipers F
  • Elferink RP
  • Rosing H
  • Beijnen JH
  • Schinkel AH

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

November 26, 2002

Associated Grants

None

Mesh Terms

  • ATP-Binding Cassette Transporters
  • Administration, Oral
  • Animals
  • Bone Marrow Transplantation
  • Cell Line
  • Chlorophyll
  • Chromatography, High Pressure Liquid
  • Dermatitis, Phototoxic
  • Diet
  • Drug Resistance
  • Female
  • Fetus
  • Fibroblasts
  • Genetic Predisposition to Disease
  • Medicago sativa
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Molecular Structure
  • Neoplasm Proteins
  • Photosensitizing Agents
  • Porphyria, Hepatoerythropoietic
  • Porphyrins
  • Pregnancy
  • Protoporphyrins
  • Radiation Chimera
  • Topotecan