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Clayton Ocular Oncology Center, Childrens Hospital of Los Angeles, and Departments of Pediatrics and Radiation Oncology [C. J. G.], University of Southern California School of Medicine, Los Angeles, California 90027
In vitro sensitivity to porphyrin-mediated photodynamic therapy (PDT) has been examined in cell lines resistant to hyperthermia. Parental (HA-1) and heat-resistant (3012) Chinese hamster fibroblasts as well as parental (RIF-1) and temperature-resistant (TR-4, TR-5, and TR-10) mouse radiation-induced fibrosarcoma cells were evaluated for thermal and PDT sensitivity. Quantitative survival curves were generated, and porphyrin uptake properties were obtained for all cell lines. Significant resistance to hyperthermia (45°C for varying exposure periods) was documented for the 3012 and temperature-resistant RIF cell strains when compared with the parent lines. Normal and heat-resistant clones, however, exhibited comparable levels of porphyrin uptake and photosensitivity. Our results indicate that cross-resistance between hyperthermia and PDT is not observed and that members of the Mr 70,000 heat shock protein family (which are elevated in the thermal-resistant cells and which may be associated with the heat-resistant phenotype) do not play a significant role in modulating PDT sensitivity. Mechanisms of in vitro cytotoxicity appear to be different for PDT and hyperthermia even though possible subcellular targets (such as the plasma membrane) and types of damage (protein denaturation) may be similar for the two modalities.
1 This investigation was performed in conjunction with the Clayton Foundation for Research and was supported in part by USPHS Grants R37-CA-31230, R01-CA-44733, and R01-CA-43087 awarded by The National Cancer Institute, Department of Health and Human Resources.
2 To whom requests for reprints should be addressed, at Clayton Ocular Oncology Center, Children's Hospital of Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027.
Received 3/ 5/90.
Revised 5/17/90.
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