DiProspero L, Singh G, Wilson B C, Rainbow A J
Department of Biology, McMaster University, Hamilton, Ont., Canada.
J Photochem Photobiol B. 1997 Apr;38(2-3):143-51. doi: 10.1016/s1011-1344(96)07462-3.
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.
光动力疗法（PDT）利用局部照射光来激活一种光敏药物（如卟吩姆钠），该药物会被肿瘤组织选择性地保留。肿瘤细胞在体外对PDT的固有敏感性被认为是临床肿瘤对PDT反应的一个重要决定因素。在这项工作中，我们展示了使用腺病毒（Ad）DNA合成的病毒能力测定作为细胞对卟吩姆钠介导的PDT敏感性和恢复情况指标的可行性。我们研究了Rif-1小鼠纤维肉瘤细胞及其对PDT耐药的衍生物Rif-8A，以及中国仓鼠卵巢（CHO）细胞和CHO-MDR多药耐药突变细胞。与这些细胞的克隆形成存活率一致，与Rif-1细胞相比，PDT处理后的Rif-8A细胞进行Ad DNA合成的能力更强；与CHO-N细胞相比，CHO-MDR细胞进行Ad DNA合成的能力更强。将Rif细胞在PDT后立即感染推迟到6小时后感染，导致Ad DNA合成能力增强，与Rif-1细胞相比，Rif-8A细胞的这种能力更强，这表明Rif-8A细胞对PDT的耐药性增加是由于PDT损伤的恢复和/或修复能力提高。与Rif-1细胞相比，紫外线照射后的Rif-8A细胞进行Ad DNA合成的能力也更强，这表明Rif-8A细胞对紫外线具有交叉耐药性。这些结果表明紫外线和PDT诱导的细胞损伤类型存在一些重叠，和/或Rif细胞中紫外线和PDT损伤的修复途径存在重叠。
