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Proceedings Paper

Studies of the significance of functional and structural changes in mitochondria in PhotofrinTM-photodynamic-therapy-resistant cells
Author(s): Brian C. Wilson; Malini Olivo; Roger Moorehead; Gurmit Singh
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Paper Abstract

This paper reports further studies of Radiation Induced Fibrosarcoma (RIF-1) tumor cells which have been made resistant to Photodynamic Therapy by multiple treatment and regrowth in vitro using the hematoporphyrin derivative photosensitizer Photofrin. Previous work has shown both structural and functional changes in the mitochondria of the resistant (RIF-8A) cells. Colocalization of Photofrin and the mitochondrial localizer Rhodamine-123 was assessed by double-label confocal fluorescence microscopy (CFM). At 18h Photofrin incubation, there was strong correlation in discrete subcellular sites between Photofrin and Rhodamine fluorescence. However, in RIF-8A cells there were also discrete regions of Rhodamine localization which showed weak or no Photofrin fluorescence. This was not observed in RIF-1 cells. CFM measurements also showed that the Photofrin fluorescence after 18h incubation was reduced by increasing concentration of Rhodamine (30 min. incubation), and that this dependence was different for the two cell types. The RIF-8A cells were also shown to be cross-resistant to cisplatin and to have an associated reduced level of Pt-DNA adducts, suggesting the possibility of increased repair capacity. Cross-resistance was not observed, however, with a ruthenium phthalocyanine photosensitizer nor, as previously reported, with other chemotherapeutic agents such as Adriamcyin. Thus, there is a complex pattern of cross-resistance with these cells. Preliminary observations of the effects of a respiratory chain inhibitor (oligomycin) and an uncoupler of oxidative phosphorylation (FCCP) indicate differences between RIF-8A and RIF-1 which may be related to the condensed mitochondrial structure of the RIF-8A cells.

Paper Details

Date Published: 19 July 1994
PDF: 8 pages
Proc. SPIE 2133, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy III, (19 July 1994); doi: 10.1117/12.179985
Show Author Affiliations
Brian C. Wilson, Univ. of Toronto Ontario Cancer Institute and Ontario Laser and Lightwave Research Ctr. (Canada)
Malini Olivo, Hamilton Regional Cancer Ctr./McMaster Univ. (Canada)
Roger Moorehead, Hamilton Regional Cancer Ctr./McMaster Univ. (Canada)
Gurmit Singh, Hamilton Regional Cancer Ctr./McMaster Univ. (Canada)

Published in SPIE Proceedings Vol. 2133:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy III
Thomas J. Dougherty, Editor(s)

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