Mitochondrial alterations in photodynamic therapy-resistant cells.
The characterization of radiation-induced fibrosarcoma cells (RIF-8A) which have been selected for resistance to Photofrin-mediated photodynamic therapy (PDT) is detailed in this report. Morphological and functional assessment of mitochondria in both the resistant RIF-8A and parental RIF-1 cells show distinct differences. Electron micrographs show that the mitochondria in the RIF-8A cells are relatively smaller; stain more densely, and display a higher cristae density than RIF-1 cells. P. A. Andrews et al. (Cancer Res., 52: 1895-1901, 1992) reported similar mitochondrial differences between a human ovarian carcinoma cell line, 2008, and its cisplatin-resistant counterpart (C13*). Dose-response curves demonstrate that these cisplatin-resistant C13* cells show cross-resistance to Photofrin-mediated PDT. Functionally, the RIF-8A cells produce more ATP and demonstrate higher succinate dehydrogenase activity than do the RIF-1 cells, but the rates of oxygen consumption do not differ between the two cell types. The PDT-sensitive RIF-1 cells demonstrate a significantly higher susceptibility to inhibition of glycolytic activity as determined by 2-deoxy-d-glucose survival curves. These findings suggest differences in the efficacy and/or mode(s) of energy production in the RIF-1 and RIF-8A cells. Since mitochondria are sensitive targets for porphyrin-mediated PDT, the observed changes in mitochondrial structure and/or function may be involved in the PDT resistance seen in RIF-8A cells.
Sharkey
S M
SM
Ontanio Cancer Foundation, Hamilton Regional Cancer Centre, Canada.
Wilson
B C
BC
Moorehead
R
R
Singh
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism / Q000494:pharmacology; D017323:Dihematoporphyrin Ether / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005354:Fibrosarcoma / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects; D010778:Photochemotherapy; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000255:Adenosine Triphosphate; D017323:Dihematoporphyrin Ether; D003847:Deoxyglucose; D013385:Succinate Dehydrogenase