Photodynamic destruction of lysosomes mediated by Nile blue photosensitizers.
Previous studies have established that a number of Nile blue derivatives are potent photosensitizers and that they are localized primarily in the lysosomes. The present study examines whether the lysosome is a main target of the photocytotoxic action mediated by these sensitizers. Chosen for this study were NBS-6I and sat-NBS, which represented, respectively, derivatives with high and moderate degrees of lysosomal. This is indicated by the light-and drug-dose-dependent losses of acid phosphatase staining particles, reduction of hexosaminidase in the lysosome-containing subcellular fraction, and impairment of the lysosomes to take up and sequester acridine orange. Ultrastructurally, swollen and ruptured lysosomes were seen as one of the first evidences of cell damage mediated by these photosensitizers. However, the study also showed that sat-NBS, which is less lysosomal selective, was less effective in mediating lysosomal destruction. Also, the degree of lysosomal destruction mediated by sat-NBS did not parallel the degree of cytotoxicity generated. This implies that for derivatives that are not exclusively localized in the lysosome, other subcellular sites may also be damaged by the photodynamic action and may play a role in the photocytotoxic process.
Urology Research Laboratory, Massachusetts General Hospital, Boston 02114.
C W
CW
Lin
J R
JR
Shulok
S D
SD
Kirley
C M
CM
Bachelder
T J
TJ
Flotte
M E
ME
Sherwood
L
L
Cincotta
J W
JW
Foley
D000135:Acid Phosphatase / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D010078:Oxazines / Q000737:chemistry / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D010078:Oxazines; D017319:Photosensitizing Agents; C008619:Nile Blue; D000135:Acid Phosphatase; D001619:beta-N-Acetylhexosaminidases