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

摘要: The breast cancer resistance protein (BCRPABCG2) is a member of the ATP-binding cassette family drug transporters and confers to various anticancer drugs. We show here that mice lacking Bcrp1Abcg2 become extremely sensitive dietary chlorophyll-breakdown product pheophorbide a, resulting in severe, sometimes lethal phototoxic lesions on light-exposed skin. Pheophorbide occurs plant-derived foods food supplements. Bcrp1 transports highly efficient limiting its uptake from ingested food. Bcrp1(-/-) also displayed previously unknown type protoporphyria. Erythrocyte levels heme precursor phototoxin protoporphyrin IX, which structurally related were increased 10-fold. Transplantation with wild-type bone marrow cured protoporphyria reduced sensitivity mice. These results indicate humans or animals low absent BCRP activity may be at risk for developing diet-dependent phototoxicity provide striking illustration importance protection toxicity normal constituents.