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Proceedings Paper

Primary targets in photochemical inactivation of cells in culture
Author(s): Kristian Berg; Stuart G. Jones; Kristian Prydz; Johan Moan
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Paper Abstract

The mechanisms of photoinactivation of NHIK 3025 cells in culture sensitized by tetrasulfonated phenylporphines (TPPS4) are described). Ultracentrifugation studies on postnuclear supernatants indicated that the intracellular distribution of TPPS4 resembles that of (beta) -N-acetyl-D-glucosaminidase ((beta) -AGA), a lysosomal marker enzyme, and that the cytosolic content of TPPS4 is below the detection limit of the ultracentrifugation method. Upon light exposure more than 90% of TPPS4 was lost from the lysosomal fractions, due to lysosomal rupture. The content of TPPS4 in the postnuclear supernatants was reduced by 30 - 40% upon exposure to light. This is most likely due to binding of TPPS4 to the nuclei, which were removed from the cell extracts before ultracentrifugation, after photochemical treatment. The unpolymerized form of tubulin seems to be an important target for the photochemical inactivation of NHIK 3025 cells. Since TPPS4 is mainly localized in lysosomes it was assumed that a dose of light disrupting a substantial number of lysosomes followed by microtubule depolymerization by nocodazole would enhance the sensitivity of the cells to photoinactivation. This was confirmed by using a colony-forming assay. The increased phototoxic effect exerted by such a treatment regime could be explained by an enhanced sensitivity of tubulin to light. Another cytosolic constituent, lactate dehydrogenase, was not photoinactivated by TPPS4 and light.

Paper Details

Date Published: 12 January 1995
PDF: 7 pages
Proc. SPIE 2325, Photodynamic Therapy of Cancer II, (12 January 1995); doi: 10.1117/12.199143
Show Author Affiliations
Kristian Berg, Institute for Cancer Research (Norway)
Stuart G. Jones, Institute for Cancer Research (Norway)
Kristian Prydz, Univ. of Oslo (Norway)
Johan Moan, Institute for Cancer Research (Norway)


Published in SPIE Proceedings Vol. 2325:
Photodynamic Therapy of Cancer II
Daniel Brault; Giulio Jori; Johan Moan; Benjamin Ehrenberg, Editor(s)

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