West C M, Moore J V
Radiobiology Department, Paterson Institute for Cancer Research, Christie Hospital, Manchester, U.K.
Int J Radiat Biol. 1988 Oct;54(4):621-34. doi: 10.1080/09553008814552061.
A comparison has been made of the in vitro light-activated drug cytotoxicities of two different porphyrin compounds, Photofrin II and TPPS4. An early passage human colon adenocarcinoma cell line, WiDr, has been exposed to either drug for 24 h, the excess drug washed from the cells and the cells irradiated with light using quartz-tungsten-halogen lamps. Neither light nor drug alone under the experimental conditions employed was toxic to WiDr cells. Together, considerable cytotoxicity could be seen and the shapes of the cell survival curves following exposure to either drug then irradiation with light, were similar. For equal amounts of drug in the medium, Photofrin II was a more efficient photosensitizer of WiDr cells than TPPS4, and differences in cellular uptake could only partly explain this. When the experimental procedure was changed by reducing the temperature of irradiation, a reduction in photosensitizing efficiency could be demonstrated. This was more pronounced for Photofrin II, and was seen as a change in the slope of the final portion of the survival curve; and as a change in the shoulder for TPPS4. Two different batches of the two drugs were compared and shown to give slightly different results for Photofrin II (change in shoulder) but not to differ for TPPS4.
对两种不同的卟啉化合物——二血卟啉醚(Photofrin II)和四磺基苯基卟啉(TPPS4)的体外光激活药物细胞毒性进行了比较。使用早期传代的人结肠腺癌细胞系WiDr,将其分别暴露于这两种药物中24小时,洗去细胞中多余的药物,然后使用石英卤钨灯对细胞进行光照。在所采用的实验条件下,单独的光照或药物对WiDr细胞均无毒性。两者共同作用时,可观察到相当大的细胞毒性,并且在暴露于任一药物后再进行光照,细胞存活曲线的形状相似。对于培养基中等量的药物,二血卟啉醚对WiDr细胞的光敏化作用比四磺基苯基卟啉更有效,细胞摄取的差异只能部分解释这一点。当通过降低光照温度改变实验程序时,可证明光敏化效率降低。这对二血卟啉醚更为明显,表现为存活曲线最后部分斜率的变化;对四磺基苯基卟啉则表现为肩部的变化。对这两种药物的两批不同批次进行了比较,结果显示二血卟啉醚有轻微差异(肩部变化),而四磺基苯基卟啉则无差异。