He J, Horng M F, Deahl J T, Oleinick N L, Evans H H
Division of Radiation Biology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4942, USA.
Photochem Photobiol. 1998 Jun;67(6):720-8.
A decrease in the efficacy of photodynamic therapy (PDT) with phthalocyanine photosensitizers was observed for lymphoblastic murine and human cell lines as the time between the addition of the photosensitizer, aluminum phthalocyanine (AIPc), to the culture medium and exposure to light was increased from 4 h to 18 h. The total intracellular concentration of photosensitizer did not decrease significantly during this 18 h interval. For the murine cell lines, the maximum cytotoxic and mutagenic effects were observed when the time between addition of the photosensitizer and irradiation was between 1 and 4 h. The time course of the variations in efficacy did not vary greatly from one murine cell line to another, even though the cell lines differ markedly in the extent of their cytotoxic and mutagenic response. The time course of the variation was similar for cytotoxicity and mutagenicity, as well as for the induction of DNA fragmentation. The human lymphoblastic cell line, WTK1, showed less variation in survival and mutability with time than did the murine cell lines. With Pc 4 (HOSiPcOSi[CH3]2[CH2]3N[CH3]2) as the photosensitizer, the photocytotoxicity for murine L5178Y (LY)-S1 cells did not change significantly as the time between addition of Pc 4 and irradiation was increased from 2 to 18 h. However, the mutagenicity decreased by a factor of three during this interval. The mutagenicity of PDT with Pc 4 was much less in LY-S1 cells than that with AlPc. The results suggest that the variation in the efficacy observed for AlPc-induced photocytotoxicity is caused by changes in the intracellular distribution and/or the aggregation of the photosensitizer with time after its addition.
随着向培养基中添加铝酞菁（AIPc）光敏剂后至光照的时间从4小时增加到18小时，在小鼠和人类淋巴细胞系中观察到酞菁光敏剂的光动力疗法（PDT）疗效下降。在此18小时期间，光敏剂的细胞内总浓度没有显著降低。对于小鼠细胞系，当添加光敏剂和照射之间的时间在1至4小时之间时，观察到最大的细胞毒性和诱变作用。尽管细胞系在细胞毒性和诱变反应程度上有显著差异，但从一个小鼠细胞系到另一个细胞系，疗效变化的时间进程差异不大。细胞毒性、诱变性以及DNA片段化诱导的变化时间进程相似。与小鼠细胞系相比，人类淋巴细胞系WTK1的存活率和变异性随时间的变化较小。以Pc 4（HOSiPcOSi[CH3]2[CH2]3N[CH3]2）作为光敏剂，当添加Pc 4和照射之间的时间从2小时增加到18小时时，对小鼠L5178Y（LY）-S1细胞的光细胞毒性没有显著变化。然而，在此期间诱变性降低了三倍。LY-S1细胞中Pc 4介导的PDT的诱变性远低于AlPc。结果表明，观察到的AlPc诱导的光细胞毒性疗效变化是由添加光敏剂后其细胞内分布和/或聚集随时间的变化引起的。
