Effect of hypothermia on the merocyanine 540-mediated purging of hematopoietic cells.
Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) inactivates experimental leukemia, lymphoma, and neuroblastoma cells by a singlet oxygen-mediated mechanism but is relatively well tolerated by normal pluripotent hematopoietic stem cells and granulocyte/macrophage progenitors (CFU-GM). MC540 is currently undergoing phase I clinical testing for the extracorporeal purging of autologous bone marrow and peripheral blood stem cells. We report here that performing MC540-mediated PDT at 4.7 degrees C (hypothermia) instead of at ambient temperature enhanced the photoinactivation of L1210 cells and CFU-GM but left the photoinactivation of K562 cells unchanged. Hypothermia reduced dye binding in K562 but not in L1210 cells, whereas the photogeneration of lipid hydroperoxides (LOOH) was affected in neither cell line. Post-PDT incubation at 4 degrees C delayed the decay of LOOH and enhanced the photoinactivation of CFU-GM as well as L1210 and K562 cells. Taken together, these results suggest that hypothermia interfered with the repair of potentially lethal photodynamic damage. They stress the importance of temperature control during and immediately after the photochemical purging of autologous bone marrow and peripheral blood stem cells.
Yamazaki
T
T
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, USA.
Sieber
F
F
D000818:Animals; D001854:Bone Marrow Cells; D016465:Bone Marrow Purging / Q000379:methods*; D016026:Bone Marrow Transplantation; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003080:Cold Temperature; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005456:Fluorescent Dyes; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007700:Kinetics; D007938:Leukemia; D007939:Leukemia L1210; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D011744:Pyrimidinones / Q000633:toxicity; D011838:Radiation-Sensitizing Agents / Q000633:toxicity; D014407:Tumor Cells, Cultured
D005456:Fluorescent Dyes; D008054:Lipid Peroxides; D011744:Pyrimidinones; D011838:Radiation-Sensitizing Agents; C003954:merocyanine dye