Photocytotoxic and DNA damaging effect of Temoporfin (mTHPC) and merocyanine 540 (MC540) on nasopharyngeal carcinoma cell

Photodynamic therapy (PDT) is a new approach to cancer treatment for a vari ety of malignant tumors. In this study, two clinical photosensitizers, Temo porfin (meta-tetra-hydroxyl-phenyl-chlorin; mTHPC) and merocyanine 540 (MC5 40), were selected to explore for their photocytotoxic and genotoxic effect s on nasopharyngeal carcinoma cells (NPC/HK1 and CNE2). Results of tetrazol ium reduction assay showed that 80% cell killing were achieved for both cel l lines at 0.4 mu g/ml mTHPC for 24 h incubation and then with 30 kJ/m(2) l ight irradiation, whereas 40 mu g/ml MC540 with 50 kJ/m(2) light dosage was required to attain the same level of phototoxicity for NPC/HK1. On the con trary, NPC/CNE2 was quite resistant to MC540. Hence, mTHPC-mediated PDT exe rted a more potent effect than MC540-mediated PDT, even though the molar ex tinction coefficient of the main absorption peak for MC540 is much higher t han that of mTHPC. Dark cytotoxicity remained negligible for both sensitize rs. Comet assay was used to evaluate the DNA strand break and potential gen otoxic effect induced by mTHPC and MC540 on the NPC cells. No DNA strand br eak was detected in the absence of light, and under sublethal treatment (LD ,,) for either sensitizer-loaded cells. Confocal laser scanning microscopy showed that mTHPC and MC540 localized in the cytoplasm but not in the nucle us of the tumor cells, which provided evidence for undetectable DNA damage under dark and low photodynamic dose. (C) 2000 Elsevier Science Ireland Ltd . All rights reserved.