Cross-resistance to photofrin-mediated photodynamic therapy and UV light and recovery from photodynamic therapy damage in Rif-8A mouse fibrosarcoma cells measured using viral capacity
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Photodynamic therapy (PDT) utilizes the localized delivery of light to activate a photosensitizing drug (such as Photofrin) which is selectively retained by the tumour tissues. The intrinsic in vitro sensitivity of tumour cells to PDT is thought to be an important determinant of clinical tumour response to PDT. In this work we show the feasibility of using a viral capacity assay for adenovirus (Ad) DNA synthesis as an indicator of cellular sensitivity to and recovery from Photofrin-mediated PDT. Rif-1 mouse fibrosarcoma cells and a PDT resistant derivative, Rif-8A, as well as Chinese hamster ovary (CHO) cells and CHO-MDR multi-drug resistant mutant cells were studied. Consistent with the clonogenic survival of these cells, the capacity of PDT-treated cells for Ad DNA synthesis was greater for Rif-8A compared to Rif-1 cells and for CHO-MDR compared to CHO-N cells. Delaying infection of the Rif cells from immediately after, to 6 hours after PDT, resulted in an increased capacity for Ad DNA synthesis, which was greater for Rif-8A compared to Rif-1 cells, suggesting that the increased resistance of Rif-8A cells to PDT results from an elevated recovery and/or repair of PDT damage. The capacity of UV-irradiated cells for Ad DNA synthesis was also greater for Rif-8A compared to Rif-1 cells indicating a cross-resistance of Rif-8A cells to UV. These results suggest some overlap in the types of cellular damage induced by UV and PDT and/or overlap in the pathways for the repair of UV and PDT damage in Rif cells.
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