On the relationship between rate of uptake of Photofrin and cellular responses to photodynamic treatment in vitro.
The Burkitt's lymphoma cell line Namalva was used as an in vitro model to study the accumulation and photocytotoxic properties of Photofrin, the photosensitizer currently in clinical trials. Photofrin uptake and intracellular protein binding were evaluated as a function of the incubation time using fluorescence spectroscopy. The drug concentration strongly affected the intracellular distribution pattern of Photofrin, which in turn was shown to correlate with the Namalva cell response to photodynamic action. At low drug load, a gradual cell response varying from transient cell cycle arrest (predominantly S-phase) to marked photocytotoxicity modulated by incubation time and light dose was observed. High drug load resulted in lethality without cell cycle selectivity. The data suggest possible Photofrin targeting of protein factors involved in cell proliferation.
Gantchev
T G
TG
Department of Nuclear Medicine and Radiobiology, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
Urumov
I J
IJ
Van Lier
J E
JE
D001693:Biological Transport, Active; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D017324:Hematoporphyrin Derivative / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010778:Photochemotherapy; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D017324:Hematoporphyrin Derivative