Photodynamic treatment with fractionated light decreases production of reactive oxygen species and cytotoxicity in vitro via regeneration of glutathione.
Photodynamic therapy removes unwanted or harmful cells by overproduction of reactive oxygen species (ROS). Fractionated light delivery in photodynamic therapy may enhance the photodynamic effect in tumor areas with insufficient blood supply by enabling the reoxygenation of the treated area. This study addresses the outcome of fractionated irradiation in an in vitro photodynamic treatment (PDT) system, where deoxygenation can be neglected. Our results show that fractionated irradiation with light/dark intervals of 45/60 s decreases ROS production and cytotoxicity of PDT. This effect can be reversed by addition of 1,3-bis-(2-chlorethyl)-1-nitrosurea (BCNU), an inhibitor of the glutathione reductase. We suggest that the dark intervals during irradiation allow the glutathione reductase to regenerate reduced glutathione (GSH), thereby rendering cells less susceptible to ROS produced by PDT compared with continuous irradiation. Our results could be of particular clinical importance for photodynamic therapy applied to well-oxygenated tumors.
Oberdanner
Christian Benno
CB
Division of Allergology and Immunology, Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
Plaetzer
Kristjan
K
Kiesslich
Tobias
T
Krammer
Barbara
B
D005978:Glutathione / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008027:Light; D009607:Nitrosourea Compounds / Q000494:pharmacology; D010778:Photochemotherapy; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000528:radiation effects; D014407:Tumor Cells, Cultured
D009607:Nitrosourea Compounds; D017382:Reactive Oxygen Species; D005978:Glutathione