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In vitro PHOTODYNAMIC EFFECTS OF LYSYL CHLORIN p 6 : CELL SURVIVAL, LOCALIZATION AND ULTRASTRUCTURAL CHANGES
Author(s) -
Leach Michael W.,
Higgins Robert J.,
Autry Susan A.,
Boggan James E.,
Lee ShwnJi H.,
Smith Kevin M.
Publication year - 1993
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1993.tb04948.x
Subject(s) - golgi apparatus , endoplasmic reticulum , cytoplasm , microbiology and biotechnology , ultrastructure , lucifer yellow , biology , mitochondrion , chemistry , anatomy , intracellular , gap junction
The in vitro cell survival, localization and ultrastructural changes following irradiation were examined in 9L glioma cells sensitized with a new photosensitizer, lysyl chlorin p 6 (LCP). In clonogenic assays, LCP was 10–100‐fold more phototoxic than photofrin II on a μg/mL basis. Lysyl chlorin p 6 uptake was blocked when cells were incubated at 2°C. In view of the chemical properties of LCP, this finding indicates that uptake probably occurred through the endocytic pathway. Fluorescence studies showed LCP localized in a region of the endocytic compartment similar in size, shape and distribution to that labeled by lucifer yellow CH (LY), as well as localizing diffusely throughout the perinuclear cytoplasm. Cells stained with both LY and LCP, however, had distinctly separate regions of staining. Lysyl chlorin p 6 localization differed from that of fluorescent probes labeling the mitochondria, Golgi apparatus and endoplasmic reticulum. Ultrastructural changes at both 2 and 30 min after laser irradiation were similar. Mitochondria were often condensed or swollen and also had constrictions and cytoplasmic invaginations. The Golgi apparatus, perinuclear space and rough endoplasmic reticulum (RER) were dilated. These data demonstrate that LCP localizes in a portion of the endosomal compartment, but that morphologic damage initially occurs in the mitochondria, Golgi apparatus and RER.