Umemura S, Yumita N, Nishigaki R
Advanced Research Laboratory, Hitachi, Ltd., Saitama.
Jpn J Cancer Res. 1993 May;84(5):582-8. doi: 10.1111/j.1349-7006.1993.tb00179.x.
Enhancement of ultrasonically induced cell damage by a gallium-porphyrin complex [ATX-70, 2,4-bis(1-decyloxyethyl)-Ga(III)-1,3,5,8- tetramethylporphryin-6,7-dipropionyl diaspartic acid] was investigated. The rate of damage to isolated sarcoma 180 cells in air-saturated suspension induced by 2 MHz ultrasound irradiation was enhanced more than four times by 80 microM ATX-70 in contrast to only twice by the same concentration of hematoporphyrin (Hp). The enhancement was almost completely inhibited in the presence of 10 mM histidine in the suspension, but not at all by 100 mM mannitol, which suggests that the enhanced cell damage was mostly mediated by singlet oxygen. Ultrasonically induced active oxygen generation in an air-saturated aqueous solution of ATX-70 was studied by detecting the electron spin resonance signals of 2,2,6,6,-tetramethyl-4-piperidone-N-oxyl produced by the reaction of 2,2,6,6-tetramethyl-4-piperidone with the generated active oxygen species. The rate of ultrasonically induced nitroxide generation was enhanced five times by 80 microM ATX-70 in contrast to only twice by Hp. The enhancement was inhibited significantly in the presence of 10 mM histidine in the suspension, but not at all by 100 mM mannitol. The singlet oxygen generation in air-saturated aqueous solution was further confirmed by the bleaching of N,N-dimethyl-4-nitrosoaniline in the presence of imidazole. The ultrasonically induced bleaching rate was enhanced six times by ATX-70, in contrast to only twice by Hp.
研究了镓卟啉配合物[ATX - 70，2,4 - 双(1 - 癸氧基乙基)-Ga(III)-1,3,5,8 - 四甲基卟啉 - 6,7 - 二丙酰天冬氨酸]对超声诱导细胞损伤的增强作用。与相同浓度的血卟啉（Hp）仅使损伤速率提高两倍相比，80 μM的ATX - 70使2 MHz超声辐照空气饱和悬浮液中分离的肉瘤180细胞的损伤速率提高了四倍多。悬浮液中存在10 mM组氨酸时，这种增强几乎完全被抑制，但100 mM甘露醇对其无抑制作用，这表明增强的细胞损伤主要由单线态氧介导。通过检测2,2,6,6 - 四甲基 - 4 - 哌啶酮与产生的活性氧物种反应生成的2,2,6,6 - 四甲基 - 4 - 哌啶酮 - N - 氧基的电子自旋共振信号，研究了ATX - 70空气饱和水溶液中超声诱导的活性氧生成。与Hp仅使生成氮氧化物的速率提高两倍相比，80 μM的ATX - 70使其提高了五倍。悬浮液中存在10 mM组氨酸时，这种增强作用被显著抑制，但100 mM甘露醇对其无抑制作用。在咪唑存在下，N，N - 二甲基 - 4 - 亚硝基苯胺的漂白进一步证实了空气饱和水溶液中单线态氧的生成。与Hp仅使超声诱导的漂白速率提高两倍相比，ATX - 70使其提高了六倍。
