Drug-induced phototoxicity evoked by inhibition of human ABC transporter ABCG2: development of in vitro high-speed screening systems.
BACKGROUND
Photosensitivity depends on both genetic and environmental factors. Pheophorbide a, present in various plant-derived foods and food supplements, can be absorbed by the small intestine. Accumulation of pheophorbide a and porphyrins in the systemic blood circulation can result in phototoxic lesions on light-exposed skin.


OBJECTIVE
As the human ATP-binding cassette (ABC) transporter ABCG2 has been suggested to be critically involved in porphyrin-mediated photosensitivity, we aimed to develop in vitro screening systems for drug-induced phototoxicity.


CONCLUSIONS
Functional impairment owing to inhibition of ABCG2 by drugs or its genetic polymorphisms can lead to the disruption of porphyrin homeostasis. This review article provides an overview on drug-induced photosensitivity, as well as our hypothesis on a potential role of ABCG2 in phototoxicity.
Tamura
Ai
A
Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology, Department of Biomolecular Engineering, 4259-B-60 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
An
Ran
R
Hagiya
Yuichiro
Y
Hoshijima
Kazuyuki
K
Yoshida
Takashi
T
Mikuriya
Kenta
K
Ishikawa
Toshihisa
T
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D019380:Anti-HIV Agents / Q000009:adverse effects; D001549:Benzamides; D017484:Dermatitis, Phototoxic / Q000209:etiology*; D024841:Fluoroquinolones / Q000009:adverse effects; D006801:Humans; D000068877:Imatinib Mesylate; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D010778:Photochemotherapy / Q000009:adverse effects; D010879:Piperazines / Q000009:adverse effects; D011110:Polymorphism, Genetic; D011166:Porphyrins / Q000378:metabolism; D011743:Pyrimidines / Q000009:adverse effects
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D019380:Anti-HIV Agents; D001549:Benzamides; D024841:Fluoroquinolones; D009363:Neoplasm Proteins; D010879:Piperazines; D011166:Porphyrins; D011743:Pyrimidines; D000068877:Imatinib Mesylate