title: Modification of extracorporeal photopheresis technology with porphyrin precursors. Comparison between 8-methoxypsoralen and hexaminolevulinate in killing human T-cell lymphoma cell lines in vitro.
abstract: BACKGROUND
  Extracorporeal photopheresis that exposes isolated white blood cells to 8-methoxypsoralen (8-MOP) and ultraviolet-A (UV-A) light is used for the management of cutaneous T-cell lymphoma and graft-versus-host disease. 8-MOP binds to DNA of both tumor and normal cells, thus increasing the risk of carcinogenesis of normal cells; and also kills both tumor and normal cells with no selectivity after UV-A irradiation. Hexaminolevulinate (HAL)-induced protoporphyrin-IX is a potent photosensitizer that localizes at membranous structures outside of the nucleus of a cell. HAL-mediated photodynamic therapy selectively destroys activated/transformed lymphocytes and induces systemic anti-tumor immunity. The aim of the present study was to explore the possibility of using HAL instead of 8-MOP to kill cells after UV-A exposure.
  
  
  METHODS
  Human T-cell lymphoma Jurkat and Karpas 299 cell lines were used to evaluate cell photoinactivation after 8-MOP and/or HAL plus UV-A light with cell proliferation and long term survival assays. The mode of cell death was also analyzed by fluorescence microscopy.
  
  
  RESULTS
  Cell proliferation was decreased by HAL/UV-A, 8-MOP/UV-A or HAL/8-MOP/UV-A. At sufficient doses, the cells were killed by all the regimens; however, the mode of cell death was dependent on the treatment conditions. 8-MOP/UV-A produced apoptotic death exclusively; whereas both apoptosis and necrosis were induced by HAL/UV-A.
  
  
  CONCLUSIONS
  8-MOP can be replaced by HAL to inactivate the Jurkat and Karpas 299 T-cell lymphoma cells after UV-A irradiation via apoptosis and necrosis. This finding may have an impact on improved efficacy of photopheresis.
authors.affiliation: Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; International Laser Centre, Bratislava, Slovakia.
authors.forename: B
authors.initials: B
authors.lastname: Cunderlíková
authors.affiliation: Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: V
authors.initials: V
authors.lastname: Vasovič
authors.affiliation: Department of Electronics and Telecommunications, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: L L
authors.initials: LL
authors.lastname: Randeberg
authors.affiliation: Department of Dermatology, St Olav's University Hospital HF, Trondheim, Norway; Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Christensen
authors.affiliation: Department of Gastric Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Warloe
authors.affiliation: Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Faculty Division, Medical Faculty, University of Oslo, Oslo, Norway.
authors.forename: J M
authors.initials: JM
authors.lastname: Nesland
authors.affiliation: Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Key Laboratory of Micro/Nano Photonics Structure (Ministry of Education), Fudan University, Shanghai, China. Electronic address: Qian.Peng@rr-research.no.
authors.forename: Q
authors.initials: Q
authors.lastname: Peng
mesh_terms: D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D019169:Jurkat Cells; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000473:pathology; D008730:Methoxsalen / Q000494:pharmacology*; D017893:Photopheresis; D017319:Photosensitizing Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester; D008730:Methoxsalen
keywords: Extracorporeal photopheresis; Hexaminolevulinate; Photodynamic therapy; Protoporphyrin IX; Psoralen; Ultraviolet-A light