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 RIS Download
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