{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:09:05Z","timestamp":1791216545561,"version":"4.1.0"},"reference-count":27,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,11,26]]},"abstract":"<jats:p>\n                    The breast cancer resistance protein (BCRP\/ABCG2) 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 Bcrp1\/Abcg2 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.\n                    <jats:italic>Bcrp1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    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\n                    <jats:italic>Bcrp1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.202607599","type":"journal-article","created":{"date-parts":[[2002,11,26]],"date-time":"2002-11-26T12:42:52Z","timestamp":1038314572000},"page":"15649-15654","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":696,"title":["The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria"],"prefix":"10.1073","volume":"99","author":[{"given":"Johan W.","family":"Jonker","sequence":"first","affiliation":[{"name":"Divisions of Experimental Therapy and Experimental Animal Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands Europe; Department of Pathology, Free University Hospital, 1081 HV Amsterdam, The Netherlands Europe; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, 9713 GZ Groningen, The Netherlands Europe; Laboratory of Experimental Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands Europe; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije","family":"Buitelaar","sequence":"additional","affiliation":[{"name":"Divisions of Experimental Therapy and Experimental Animal Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands Europe; Department of Pathology, Free University Hospital, 1081 HV Amsterdam, The Netherlands Europe; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, 9713 GZ Groningen, The Netherlands Europe; Laboratory of Experimental Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands Europe; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Els","family":"Wagenaar","sequence":"additional","affiliation":[{"name":"Divisions of Experimental Therapy and Experimental Animal Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands Europe; Department of Pathology, Free University Hospital, 1081 HV Amsterdam, The Netherlands Europe; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, 9713 GZ Groningen, The Netherlands Europe; Laboratory of Experimental Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands Europe; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin A.","family":"van der Valk","sequence":"additional","affiliation":[{"name":"Divisions of Experimental Therapy and Experimental Animal Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands Europe; Department of Pathology, Free University Hospital, 1081 HV Amsterdam, The Netherlands Europe; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, 9713 GZ Groningen, The Netherlands Europe; Laboratory of Experimental Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands Europe; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George L.","family":"Scheffer","sequence":"additional","affiliation":[{"name":"Divisions of Experimental Therapy and Experimental Animal Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands Europe; Department of Pathology, Free University Hospital, 1081 HV Amsterdam, The Netherlands Europe; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, 9713 GZ Groningen, The Netherlands Europe; Laboratory of Experimental Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands Europe; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik J.","family":"Scheper","sequence":"additional","affiliation":[{"name":"Divisions of Experimental Therapy and Experimental Animal Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands Europe; Department of Pathology, Free University Hospital, 1081 HV Amsterdam, The Netherlands Europe; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, 9713 GZ Groningen, The Netherlands Europe; Laboratory of Experimental Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands Europe; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Pl\u00f6sch","sequence":"additional","affiliation":[{"name":"Divisions of Experimental Therapy and Experimental Animal Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands Europe; Department of Pathology, Free University Hospital, 1081 HV Amsterdam, The Netherlands Europe; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, 9713 GZ Groningen, The Netherlands Europe; Laboratory of Experimental Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands Europe; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folkert","family":"Kuipers","sequence":"additional","affiliation":[{"name":"Divisions of Experimental Therapy and Experimental Animal Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands Europe; Department of Pathology, Free University Hospital, 1081 HV Amsterdam, The Netherlands Europe; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, 9713 GZ Groningen, The Netherlands Europe; Laboratory of Experimental Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands Europe; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald P. 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